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[ "11966543", "14572560", "9440631", "15647648", "7904847", "8284627", "8759659", "11007222", "10692734" ]

[ "Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease.", "Eradication of Helicobacter pylori improves the healing rate and reduces the relapse rate of nonbleeding ulcers in patients with bleeding peptic ulcer.", "One-week antibiotics versus maintenance acid suppression therapy for Helicobacter pylori-associated peptic ulcer bleeding.", "Helicobacter pylori eradication as the sole treatment for gastric and duodenal ulcers.", "Eradication of Helicobacter pylori infection and the recurrence of duodenal ulcers.", "Treatment of Helicobacter pylori reduces the rate of rebleeding in peptic ulcer disease.", "Antimicrobial therapy for Helicobacter pylori infection versus long-term maintenance antisecretion treatment in the prevention of recurrent hemorrhage from peptic ulcer: prospective nonrandomized trial on 125 patients.", "Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage--a long-term randomized, controlled study.", "Does the eradication of Helicobacter pylori cure duodenal ulcer disease in communities with a high prevalence rate? Comparison with long-term acid suppression." ]

[ "The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long-term outcome.\n To evaluate the relapse rate of peptic ulcer in the long-term follow-up of patients after H. pylori eradication therapy.\n Patients infected with H. pylori (445; 88 duodenal ulcer, 357 gastric ulcer) were randomly divided into three groups. In group A, patients received 'conventional treatment' including acid decreasing therapy with a histamine H2-receptor antagonist or proton pump inhibitor (PPI). In group B, patients received 'dual therapy' including one antibiotic plus acid-decreasing therapy. In group C, patients received 'triple therapy' with PPI plus amoxicillin and clarithromycin. Eradication of H. pylori infection was assessed by histology of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12 months after stopping therapy. Endoscopy was performed at intervals of 6 months for 5 years.\n Intention-to-treat eradication rates for the duodenal ulcer patients were 0% for group A, 46% for group B and 80% for group C; eradication rates for the gastric ulcer patients were 0%, 33% and 83% respectively. No recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers recurred after successful eradication during follow-up for 5 years. In contrast, in patients with persistent H. pylori infection all DU and 92% of gastric ulcers recurred.\n Eradication of H. pylori infection changes the natural course of peptic ulcer.", "A causal relationship between Helicobacter pylori (H. pylori) and peptic ulcer complications remains obscure. The aim of this study was to determine the importance of H. pylori and other risk factors for healing rate, ulcer recurrence, and rebleeding in patients with bleeding peptic ulcer.\n A total of 223 patients with H. pylori positive bleeding peptic ulcer were randomly allocated to three treatment groups: 1) quadruple therapy (QT) (88 patients); 2) dual therapy (DT) (88 patients); and 3) omeprazole and placebo therapy (OPl) (47 patients). Endoscopic assessment was performed initially and at 8 and 52 wk. Ulcer healing and eradication rates were assessed; endpoints were ulcer relapse and ulcer rebleeding during 52 wk.\n Results after 8 and 52 wk were available for 211 and 179 patients, respectively. Eradication rate was 100% (95% CI = 96-100%) in the QT, 84% (95% CI = 74-91%) in the DT, and 4% (95% CI = 1-15%) in the OPl group. Ulcer healing rate was 95% (95% CI = 91-98%) in H. pylori negative and 8% (95% CI = 70-91%) in H. pylori positive patients. Ulcer relapses occurred in 2% (95% CI = 0.5-6%) of H. pylori negative and in 38% (95% CI = 24-54%) of H. pylori positive patients, and rebleeding occurred in five patients (three H. pylori positive and two negative).\n Eradication of H. pylori infection enhances healing of bleeding peptic ulcers after endoscopic therapy. H. pylori infection is an important independent risk factor for relapsing of nonbleeding ulcers in patients with bleeding peptic ulcer.", "Bleeding peptic ulcer is the most important cause of upper gastrointestinal bleeding. Our aim was to compare the effect of anti-Helicobacter therapy with maintenance treatment of H2-receptor antagonist in the prevention of relapses of ulcer and bleeding. Patients with bleeding duodenal or gastric ulcers and H. pylori infection were randomized to receive either a one-week course of triple therapy with bismuth subcitrate, metronidazole, and tetracycline plus ranitidine or a six-week course of ranitidine 300 mg/day. After the ulcers healed, the antibiotic-treated patients were not given any medication, whereas the ranitidine-treated patients continued to receive a maintenance dose of 150 mg/day. One hundred twenty-six patients were randomized to receive anti-Helicobacter therapy and 124 patients to receive long-term ranitidine. H. pylori eradication was achieved in 98.2% in those who received triple therapy and 6.1% in those who received ranitidine (P < 0.0001). At the six-week follow-up, ulcer healing was documented in 88.2% in those who received triple therapy and 86.1% in those who received ranitidine (P = 0.639). Recurrent ulcer developed in nine of the ranitidine-treated patients and three of them presented with recurrent upper gastrointestinal bleeding. One patient in the antibiotic group developed recurrent ulcer without rebleeding (P = 0.01). It is concluded that eradication of H. pylori is sufficient for the prevention of recurrent bleeding ulcers.", "It is uncertain whether eradication of Helicobacter pylori--without a prolonged suppression of acid secretion--is sufficient to allow healing of peptic ulcers. We evaluated whether eradication of H. pylori with no following anti-secretory medication then administered is sufficient for treatment of peptic ulcers. We also looked at the impact of non-steroidal anti-inflammatory drug (NSAID) and acetylsalicylic acid (ASA) use on ulcer relapses.\n The effect of eradication on ulcer healing and relapse rate was analysed in 115 patients, randomly allocated to four treatment groups: (1) quadruple therapy (28); (2) dual therapy (n-30); (3) triple therapy (n=27); and (4) lansoprazole and placebo (n=30). Endoscopic assessment was performed at 0, 8, and 52 weeks.\n The ulcer healing rate was 100% [95% confidence interval (CI), 95-100%] in H. pylori-negative and 83% (95% CI, 67-94%) in H. pylori-positive patients (P<0.01). In patients who used NSAIDS or ASA, the healing rates was 100% (95% CI, 73-100%) and 75% (95% CI, 19-99%) in H. pylori-negative (12 patients) and H. pylori-positive patients (four patients) (P = not significant). Ulcer relapses occurred in 5% (95% CI, 1-13%) of H. pylori-negative and in 36% (95% CI, 19-56%) of H. pylori-positive patients (P < 0.01). In H. pylori-negative patients who used NSAIDs or ASA the ulcer relapse rate was 30% (95% CI, 7-65%), whereas the ulcer relapse rate was 2% (95% CI, 0.4-10%) in patients who did not use NSAIDs or ASA (P < 0.05). No difference in ulcer relapse rate in H. pylori-positive patients who used or did not use NSAIDs or ASA was found. The eradication rate of H. pylori was 93% (95% CI, 76-99%) in the quadruple therapy group, 83% (95% CI, 64-94%) in the dual therapy group, 100% (95% CI, 87-100%) in the triple therapy group, and 0% (95% CI, 0-12%) in the lansoprazole and placebo group.\n Eradication treatment for H. pylori-positive gastric or duodenal ulcer is sufficient, with no need to follow it with anti-secretory medication. Cure of the infection reduces ulcer relapses in patients who did not use NSAIDs or ASA.", "The purpose of this study was to compare the performance of different regimens on Helicobacter pylori (H. pylori) eradication and duodenal ulcer recurrence. During a four-week period, 59 patients with duodenal ulcers who were positive for H. pylori infection were randomly treated with one of three regimens. Seventeen patients were treated with ranitidine, 19 with colloidal bismuth subcitrate (CBS), and 23 with triple therapy (CBS, tetracycline and metronidazole). Forty-six patients with healed ulcers after treatment received follow-up for six months without maintenance therapy. The recurrence rates of duodenal ulcers confirmed by endoscopy in these three groups were 64%, 33% and 0% at the third month, and 73%, 67% and 5% at the sixth month, respectively. In the ranitidine therapy group, H. pylori infection was still present at the final follow-up. In the CBS therapy group, H. pylori was suppressed initially, but recurred in all cases. In the triple therapy group, there was only one case in which H. pylori infection persisted and where ulcer recurrence occurred after 3.5 months. The remaining cases were all H. pylori negative and had no recurrence of duodenal ulcers during the six months of follow-up. Overall, 19/27 (70%) patients positive for H. pylori had a recurrence of duodenal ulcers, while none of the 19 patients who were negative for H. pylori had a recurrence of ulcers at the sixth month. This study shows that triple therapy is more effective than the other two regimens in the eradication of H. pylori and in reducing the recurrence of ulcers. H. pylori may play a role in the recurrence of the duodenal ulcer.", "We evaluated whether therapy designed to eradicate Helicobacter pylori infection resulted in a reduction in rebleeding in patients with peptic ulcer disease. Patients presenting because of major upper gastrointestinal hemorrhage from peptic ulcer and whose ulcers healed in a study in which they were randomized to receive ranitidine alone or triple therapy plus ranitidine were followed up regularly with endoscopy. No maintenance anti-ulcer therapy was given after ulcer healing.\n Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet), and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. Development of ulcer recurrence with or without recurrent upper gastrointestinal bleeding was evaluated.\n Thirty-one patients with major upper gastrointestinal bleeding from peptic ulcer were studied; 17 received triple therapy and 14 ranitidine alone. Major rebleeding occurred significantly (p = 0.031) more often in those in the ranitidine group (28.6%), compared with none (0%) in the triple therapy group.\n Eradication of H. pylori infection reduces the rate of ulcer recurrence and rebleeding in complicated ulcer disease.", "Our objective was to assess the effectiveness of therapy for Helicobacter pylori (HP) on the prevention of recurrent bleeding in patients with recent upper gastrointestinal hemorrhage from peptic ulcers.\n We performed a prospective follow-up study without randomization on 125 consecutive patients (83 males and 42 females) who had presented with their first major episode of upper gastrointestinal hemorrhage from peptic ulcer (22 gastric and 103 duodenal ulcers). All 125 patients were HP-positive. During the acute phase of bleeding, all patients were treated with standard supportive measures. After the acute bleeding phase, patients were allocated to two treatment groups: 1) antimicrobial therapy-84 patients received one of the following three regimens: 1) amoxicillin 500 mg t.i.d. for 10 days + omeprazole 20 mg b.i.d. for 30 days; 2) clarythromycin 500 mg t.i.d. for 12 days + omeprazole 20 mg b.i.d. for 30 days; or 3) amoxicillin 500 mg t.i.d. for 10 days + metronidazole 500 mg t.i.d. for 10 days + colloidal bismuth subcitrate 240 mg b.i.d. for 30 days. For long-term antisecretion maintenance treatment, 41 patients were allocated to either omeprazole 20 mg once a day or ranitidine 150 mg once a day, for 1 yr.\n During the follow-up period, peptic ulcers recurred in six patients in the antibiotic group (7.14%) and 13 patients in the maintenance group (31.7%) (p < 0.001). The fraction of patients without recurrent bleeding was greater in the antibiotic group than in the maintenance group. Two patients in the antibiotic group (2.3%) and five in the maintenance group (12.1%) had recurrent hemorrhages (p < 0.1).\n Cure of HP infection reduces the recurrence of peptic ulcer and of rebleeding from ulcer disease more effectively than does long-term maintenance therapy.", "Eradication of Helicobacter pylori (H. pylori) in patients with uncomplicated duodenal ulcers prevents long-term recurrence of ulcers. We aimed to study whether treatment of H. pylori prevents the long-term recurrence of duodenal ulcer hemorrhage.\n Patients with duodenal ulcer bleeding and confirmed H. pylori infection were recruited. A total of 120 patients were randomly assigned to triple therapy (DeNoltab 120 mg, amoxycillin 500 mg, and metronidazole 300 mg four times daily) or DeNoltab 120 mg four times daily alone. No maintenance therapy was given during the follow-up period. The endpoints were the cumulative rates of symptomatic and bleeding duodenal ulcer recurrences.\n Of the patients receiving the triple regimen, 85.1% had H. pylori eradicated as compared to 2.0% of patients receiving DeNoltab (p < 0.05). More patients in the DeNoltab group than those in the Triple group had recurrence of ulcer bleeding, but this did not reach statistical significance (12/60 vs 6/60, p = 0.20). Logistic regression analysis on clinical, personal, and endoscopic characteristics identified persistent H. pylori infection as the only independent predictor of recurrence of duodenal ulcer bleeding.\n Treatment of H. pylori alone with the present bismuth-based triple therapy in patients with duodenal ulcer hemorrhage did not result in significant reduction in further bleeding episodes, although a trend was seen for the group that was given triple therapy. On the other hand, posttreatment H. pylori status was found to be an independent predictor of bleeding recurrence.", "The long-term effect of Helicobacter pylori eradication on the natural history of duodenal ulcer has been investigated and compared with long-term acid suppression treatment in an endemic community for infection. Seventy-three patients with endoscopically verified H. pylori positive active duodenal ulcer disease were included in this prospective study. Patients were divided into two groups. Group A patients (n = 39) were given an omeprazole-based triple eradication regimen, while group B patients (n = 34) were given omeprazole alone followed by long-term famotidine 20 mg daily as maintenance treatment. A control endoscopy was performed at the third month of treatment. The bacterium was eradicated in 32 (82%) of group A patients. All patients were followed up for two years and an endoscopy performed at the end of each year. H. pylori recurred in 13 patients and the reinfection rate was 44.8% over two years. Duodenal ulcer recurred in seven of these patients at two years (24.1%). There was a close association between H. pylori reinfection and ulcer relapse. Group B patients remained H. pylori positive during the study and the ulcer recurred in five of these patients (6.6%) despite continuous famotidine treatment. There was no statistically significant difference in ulcer relapse rate between the groups. These results suggested that H. pylori eradication is not an absolute solution for duodenal ulcer disease in high endemic regions and continuous maintenance treatment with H2-receptor antagonists is still an alternative approach in some chronic recurrent cases." ]

[ "16076335", "10449846", "17277653", "17698432", "16749570", "12960786", "9171125", "7577282", "9322475" ]

[ "Randomized, prospective comparison of postoperative pain in low- versus high-pressure pneumoperitoneum.", "Randomized comparison between low-pressure laparoscopic cholecystectomy and gasless laparoscopic cholecystectomy.", "Prospective randomized trial on low-pressure versus standard-pressure pneumoperitoneum in outpatient laparoscopic cholecystectomy.", "Randomized trial of low-pressure carbon dioxide-elicited pneumoperitoneum versus abdominal wall lifting for laparoscopic cholecystectomy.", "Lactate and acid base changes during laparoscopic cholecystectomy.", "Randomized comparison between different insufflation pressures for laparoscopic cholecystectomy.", "Laparoscopic cholecystectomy using abdominal wall retraction. Hemodynamics and gas exchange, a comparison with conventional pneumoperitoneum.", "Conventional pneumoperitoneum compared with abdominal wall lift for laparoscopic cholecystectomy.", "Splanchnic and renal deterioration during and after laparoscopic cholecystectomy: a comparison of the carbon dioxide pneumoperitoneum and the abdominal wall lift method." ]

[ "Reduced postoperative pain after laparoscopic cholecystectomy (LC) compared to open cholecystectomy (OC) may be able to be further optimized. To reduce pain, focus should be directed on the effects of individual components of pain.\n A double-blind, randomized, controlled trial was carried out in a tertiary care hospital. Fifty-three elective patients with symptomatic gallstones were enrolled into the study. Patients were randomized to low- or high-pressure pneumoperitoneum groups. In all patients, gas pressure was set to 15 mmHg during placement of ports. Later on, in the low-pressure group, the rest of the procedure was performed at 10 mmHg pressure. At 6 and 24 h postoperatively, a short-form McGill Questionnaire (MPQ) was obtained from all patients. Patients were then asked to complete a 10-cm visual analogue scale (VAS) for abdominal pain.\n Pain scores were generally low for both groups. Statistical comparisons of mean cumulative McGill score and VAS abdominal pain scores in both groups did not reach statistical significance at 6 and 24 h after operation.\n There was no correlation between high- and low-pressure laparoscopy and postoperative pain after LC. Peritoneal stretching may be more responsible for shoulder pain but has less effect on intensity of abdominal pain or incisional pain. On the basis of these negative findings, routine use of low-pressure pneumoperitoneum for alleviation of postoperative pain following LC is not recommended.", "Laparoscopic cholecystectomy using low-pressure pneumoperitoneum (8 mmHg) minimizes adverse hemodynamic effects, reduces postoperative pain, and accelerates recovery. Similar claims are made for gasless laparoscopy using abdominal wall lifting. The aim of this study was to compare gasless laparoscopic cholecystectomy to low-pressure cholecystectomy with respect to postoperative pain and recovery.\n Thirty-six patients were randomized to low-pressure or gasless laparoscopic cholecystectomy using a subcutaneous lifting system (Laparotenser).\n The characteristics of the patients were similar in the two groups. The procedure was completed in all patients in the low-pressure group, but two patients in the gasless group were converted to pneumoperitoneum. There were no significant differences in postoperative pain and analgesic consumption, but patients in the gasless group developed shoulder pain more frequently (50% vs 11%, p < 0.05). Gasless operation took longer to perform (95 vs 72.5 min, p = 0.01).\n Gasless and low-pressure laparoscopic cholecystectomy were similar with respect to postoperative pain and recovery. The gasless technique provided inferior exposure and the operation took longer, but the technique may still have value in high-risk patients with cardiorespiratory disease.", "Inpatient low-pressure pneumoperitoneum laparoscopic cholecystectomy (LPLC) has been shown to have less postoperative pain (especially shoulder-tip pain). No report so far has documented the use of lower-pressure pneumoperitoneum in outpatient laparoscopic cholecystectomy (LC). A prospective randomized trial was conducted in Tung Wah Hospital, Day Surgery Centre from January 2004 to December 2004. A total of 40 patients were recruited and 20 of whom were allocated to each arm. Outcome measures included operation time, treatment-related morbidity, mortality, postoperative pain (eg, shoulder-tip pain), consumption of analgesics, and level of satisfaction. All patients in both groups could be discharged on the same day. Patients' demographics and operation time were comparable in both groups. There were no treatment-related morbidity and mortality, nor was there any significant difference in postoperative pain. Less shoulder-tip pain was observed in the LPLC group though without significant difference (5% vs. 20%; P=0.151). Three patients in the LPLC group needed higher insufflation pressure (12 mm Hg) because of inadequate exposure and adhesions, and the operations were successful in all of them. Otherwise, no conversion to open procedure was noted in both groups. The consumption of analgesics was minimal and a high level of satisfaction was achieved in both groups of patients. The present study demonstrated no difference in LPLC and standard-pressure pneumoperitoneum laparoscopic cholecystectomy in the outcomes of outpatient LC. Routine use of lower-pressure pneumoperitoneum in outpatient LC would not be recommended unless in selected straightforward cases.", "Two alternative surgical techniques for elective laparoscopic cholecystectomy (LC), low-pressure insufflation of the peritoneal cavity and abdominal wall lifting (AWL), have been developed over time to minimize the disadvantages associated with CO2-elicited pneumoperitoneum. To the best of our knowledge, the 2 methods have seldom been compared as regards their relative advantages and disadvantages.\n Eighty patients scheduled for elective LC were randomized into either a low-pressure (8 mmHg) CO2 insufflation method (LPLC) group, or a gasless technique using a subcutaneous abdominal wall lifting device (GLC group). The duration of the surgical procedure, the surgical results including level of postoperative pain, and perioperative cardiopulmonary function changes experienced by the members of both groups were compared.\n Laparoscopic surgery was completed for all but 1 patient from each group due to an inadequate surgical-site exposure. There was no mortality for study participants, and no major complications were noted for members of either group. The LPLC group evidenced a shorter surgical duration as compared to the GLC group (77 +/- 28 minutes vs. 98 +/- 27 minutes, respectively; p < 0.01) and a lower incidence of postoperative shoulder pain (2/38 vs. 8/39, respectively; p < 0.05), although significant differences in intraoperative pulmonary function were noted (an increased PaCO2, Pet CO2 and peak-airway pressure and decreased arterial blood pH; p < 0.01) for the LPLC group compared to the GLC group.\n Both alternative methods for this type of surgery appeared feasible and safe for LC. Low-pressure CO2 pneumoperitoneum had a shorter surgical duration and less postoperative shoulder pain compared to the GLC technique, but did not feature any other advantage over the AWL technique with regard to impact on cardiopulmonary function.", "The observation of hemodynamic and metabolic impairment related to CO2 pneumoperitoneum and postoperative mesenteric ischemia reports following laparoscopic procedures have raised concern about local and systemic effects of increase intraabdominal pressure during laparoscopic procedures. The present study aims to evaluate the metabolic and acid base responses of using high pressure versus low pressure pneumoperitonium in patients undergoing laparoscopic cholecystectomy in a prospective randomized clinical trial.\n 20 ASA I-II patients scheduled for elective laparoscopic cholecystectomy were randomly allocated to one of two study groups; high pressure pneumoperitoneum 12-14mmHg (HPP, n=10) versus low pressure pneumoperitoneum 6-8mmHg (LPP, n=10) undergoing laparoscopic cholecystectomy. Arterial blood gases and lactate levels were determined after induction of anesthesia (before pneumoperitonium), then after 10 min, then 30 min after insufflations and at the end of surgery and 1 hour postoperatively. Nurses in recovery unit reported pain assessment starting postoperatively until 3 hours on a 10mm VAS (0-10). Statistical significant was established at P<0.05.\n Bicarbonate was significantly (P>0.0412) lower in high pressure group at 30 min and 60 min after insufflations. In high pressure group lactate levels increased significantly as compared to low pressure group, (at 30 minutes after the establishment of abdominal pneumatic inflation P<0.006 and remained significantly increased (P<0.001) until the end of surgery and one hour thereafter) (P<0.001). The mean postoperative pain score during second hour (VAS) at HPP group was 7.4 +/- 1.17 which is significantly (P < or = 0.006) higher than pain score in LPP group 5.0 +/- 1.886. Shoulder tip pain was reported in 3 patients in the high pressure group and only one patient in the lower pressure group.\n High-pressure pneumoperitonium causes statistically significant elevation in the arterial lactate level intraoperatively until one hour post operatively. It also causes higher pain score and shoulder tip pain.", "Laparoscopy using carbon dioxide insufflation induces adverse effects in both the cardiovascular and the respiratory function. The use of low pressure pneumoperitoneum has been shown to reduce adverse hemodynamic effects. However, its effect on tissue trauma and postoperative pain and recovery remains controversial. The aim of this study was to compare tissue trauma, postoperative pain, and recovery in two groups of patients undergoing laparoscopic cholecystectomy, one at insufflation pressure of 8 (LC8) and the other at 15 mm Hg (LC15). Forty patients were randomized, 20 in each group. The characteristics of the patients were similar in the two groups. The procedure was completed in all patients in the LC15 group, but in 2 patients in the LC8 group the pressure was increased to 15 mm Hg to complete the operation. There were no significant differences in postoperative pain scores, analgesic consumption, and the incidence of nausea, vomiting, and shoulder pain between the two groups. C-reactive protein concentrations and white blood cell count rose significantly after surgery, but the increase was similar in the two groups. The median duration of surgery was similar, 23 minutes (range 15-65) in the LC8 group and 25 minutes (range 15-80) in the LC15 group. Using our technique of laparoscopic cholecystectomy, there were no advantages to tissue damage, postoperative pain, and recovery when a low pressure pneumoperitoneum was used.", "Disadvantages related to CO2 pneumoperitoneum have led to development of the abdominal wall retractor (AWR), a device designed to facilitate laparoscopic surgery without conventional pneumoperitoneum (15 mmHg CO2). We investigated the effects of the AWR on hemodynamics and gas exchange in humans. We also investigated whether the use of an AWR imposed extra technical difficulties for the surgeon. A pilot study revealed that cholecystectomy without low-pressure pneumoperitoneum was technically impossible.\n A prospective randomized controlled trial: Twenty patients undergoing laparoscopic cholecystectomy were randomly allocated into group 1: AWR with low-pressure pneumoperitoneum (5 mmHg), or group 2: conventional pneumoperitoneum (15 mmHg).\n Surgery using the AWR lasted longer, 72 +/- 16 min (mean +/- SD) vs 50 +/- 18 min compared with standard laparoscopic cholecystectomy. There were no differences between the groups with respect to hemodynamic parameters, although a small reduction of the cardiac output was observed using conventional pneumoperitoneum (from 3.9 +/- 0.7 to 3. 2 +/- 1.1 l/min) and an increase during AWR (from 4.2 +/- 0.9 to 5.2 +/- 1.5 l/min). Peak inspiratory pressures were significantly higher during conventional pneumoperitoneum compared to AWR. A slight decrease in pH accompanied by an increase in CO2 developed during pneumoperitoneum and during the use of the AWR. In both groups arterial PO2 decreased.\n The results indicate that the view was impaired during use of the AWR and therefore its use was difficult and time-consuming. Possible advantages of this devices' effects on hemodynamics and ventilatory parameters could not be confirmed in this study.", "We have compared, in a randomized study, conventional carbon dioxide pneumoperitoneum with abdominal wall lift in 25 patients undergoing laparoscopic cholecystectomy. Intra-abdominal pressure (IAP) (11 (SD 2) mm Hg vs 2.7 (9) mm Hg) (P < 0.01) and total amount of carbon dioxide used (40 (23) litre vs 9 (7) litre) (P < 0.001) were significantly less with abdominal wall lift. Pulmonary compliance was significantly greater (P < 0.01) in the abdominal wall lift group throughout operation. During the first 15 min of insufflation, arterial pressures were lower with abdominal wall lift (P < 0.05). In the conventional pneumoperitoneum group, femoral vein pressure increased (P < 0.01) and remained elevated for 3 h in the recovery room. Postoperative drowsiness was of significantly longer duration in the conventional pneumoperitoneum group than in the abdominal wall lift group (98 (46) min vs 13 (34) min) (P < 0.01). Postoperative nausea and vomiting and right shoulder pain occurred more often in patients with conventional pneumoperitoneum (P < 0.05). We conclude that the benefits of abdominal wall lift may be attributed to avoiding excessive carbon dioxide and high IAP.", "Carbon dioxide (CO2) pneumoperitoneum together with an increased intraabdominal pressure (IAP) induces a hemodynamic stress response, diminishes urine output, and may compromise splanchnic perfusion. A new retractor method may be less traumatic. Accordingly, 30 ASA physical status I or II patients undergoing laparoscopic cholecystectomy were randomly allocated to a CO2 pneumoperitoneum (IAP 12-13 mm Hg) (control) or to a gasless abdominal wall lift method (retractor) group. Anesthesia and intravascular fluids were standardized. Direct mean arterial pressure (MAP), urine output, urine-N-acetyl-beta-D-glucosaminidase (U-NAG), arterial blood gases, gastric mucosal PCO2, and intramucosal pH (pHi) were measured. Normoventilation was instituted in all patients. MAP increased (P < 0.001) only with CO2 pneumoperitoneum. Minute volume of ventilation had to be increased by 35% with CO2 insufflation. PaCO2 was significantly higher (P < 0.05) for 3 h postoperatively in the control group. Diuresis was less (P < 0.01) and U-NAG levels (P < 0.01) higher in the control group. The pHi decreased after induction of pneumoperitoneum up to three hours postoperatively and remained intact in the retractor group. We conclude that the retractor method for laparoscopic cholecystectomy ensures stable hemodynamics, prevents respiratory acidosis, and provides protection against biochemical effects, which reveal the renal and splanchic ischemia caused by CO2 insufflation. Implications: A mechanical retractor method (gasless) was compared with conventional CO2 pneumoperitoneum for laparoscopic cholestectomy. The gasless method ensured stable hemodynamics, prevented respiratory acidosis, and provided protection against the renal and splanchnic ischemia seen with CO2 pneumoperitoneum." ]

[ "20626310", "18647729", "8747817", "21281410", "2206966", "6842217", "11215597", "21239366", "6202993" ]

[ "The effectiveness of traditional methods and altered auditory feedback in improving speech rate and intelligibility in speakers with Parkinson's disease.", "Design and methods of a randomized controlled trial on early speech and language therapy in patients with acute stroke and aphasia.", "Comparison of two forms of intensive speech treatment for Parkinson disease.", "Treating disordered speech and voice in Parkinson's disease online: a randomized controlled non-inferiority trial.", "Speech therapy and Parkinson's disease: a review and further data.", "Speech therapy for Parkinson's disease.", "Changes in vocal loudness following intensive voice treatment (LSVT) in individuals with Parkinson's disease: a comparison with untreated patients and normal age-matched controls.", "Oral reading for language in aphasia (ORLA): evaluating the efficacy of computer-delivered therapy in chronic nonfluent aphasia.", "Effectiveness of speech therapy for aphasic stroke patients. A randomised controlled trial." ]

[ "Communication problems are a frequent symptom for people with Parkinson's disease (PD) which can have a significant impact on their quality-of-life. Deciding on the right management approach can be problematic though, as, with the exception of LSVT, very few studies have been published demonstrating the effectiveness of treatment techniques. The aim of this study was to compare traditional rate reduction methods with altered auditory feedback (AAF) with respect to their effectiveness to reduce speech rate and improve intelligibility in speakers with PD. Ten participants underwent both types of treatments in once weekly sessions for 6 weeks. Outcomes measures were speech rate for passage reading as well as intelligibility on both a passage reading and a monologue task. The results showed that, as a group, there was no significant change in either speech rate or intelligibility resulting from either treatment type. However, individual speakers showed improvements in speech performance as a result of each therapy technique. In most cases, these benefits persisted for at least 6 months post-treatment. Possible reasons for the variable response to treatment, as well as issues to consider when planning to use AAF devices in treatment are discussed.", "Most clinicians would recommend speech and language therapy (SLT) for aphasic patients. The question of when and for how long SLT should be administered still remains controversial. The aim of this trial is to evaluate the efficacy of early SLT in patients with acute stroke and aphasia in a randomized controlled trial. This report will present design and methods and discuss feasibility.\n Consecutive patients with first ever ischemic stroke and aphasia are assessed by the Amsterdam-Nijmegen Everyday Language Test (ANELT) and a short version of the Norsk Grunntest for Afasi. The treatment is language enrichment therapy, and the therapy is given 45 min/day for 15 weekdays. The primary outcome is the difference in the degree of aphasia between the SLT treated group and the control group measured by ANELT at 3 weeks.\n Around 10% of acute consecutive patients with aphasia are included. Of the first 79 included patients, 86% have completed the study according to protocol. We intend to include 125 patients, which provide sufficient statistical power to detect a clinically significant difference in the degree of aphasia.\n It is feasible to conduct a randomized controlled study on very early SLT for acute aphasic patients.", "This study investigated the effect of two forms of intensive speech treatment, (a) respiration (R) and (b) voice and respiration (Lee Silverman Voice Treatment [LSVT]), on the speech and voice deficits associated with idiopathic Parkinson disease. Forty-five subjects with Idiopathic Parkinson disease completed extensive pretreatment neurological, otolaryngological, neuropsychological, and speech assessments. All subjects completed 16 sessions of intensive speech treatment, 4 times a week for 1 month. Pre- and post-treatment measures included intensity and maximum duration during sustained vowel phonation. Intensity, habitual fundamental frequency, fundamental frequency variability, and utterance and pause duration were measured during reading of the \"Rainbow Passage\" and conversational monologue as well. Family and subject self-ratings were completed pre- and post-treatment for the perceptual variables loudness, monotonicity, hoarseness, overall intelligibility, and initiation of conversation. Significant pre- to post-treatment improvements were observed for more variables and were of greater magnitude for the subjects who received the voice and respiration treatment (LSVT). Only subjects who received the LSVT rated a significant decrease post-treatment on the impact of Parkinson disease on their communication. Correlations between descriptive prognostic variables (i.e., stage of disease, speech/voice severity rating, depression, and time since diagnosis) and magnitude of treatment-related change indicated these factors did not significantly predict treatment effectiveness. These findings suggest that intensive voice and respiration (LSVT) treatment, focusing on increased vocal fold adduction and respiration, is more effective than respiration (R) treatment alone for improving vocal intensity and decreasing the impact of Parkinson disease on communication.", "Telerehabilitation may be a feasible solution to the current problems faced by people with Parkinson's disease in accessing speech pathology services.\n To investigate the validity and reliability of online delivery of the Lee Silverman Voice Treatment (LSVT®) for the speech and voice disorder associated with Parkinson's disease.\n Thirty-four participants with Parkinson's disease and mild-to-moderate hypokinetic dysarthria took part in the randomized controlled non-inferiority laboratory trial and received the LSVT® in either the online or the face-to-face environment. Online sessions were conducted via two personal computer-based videoconferencing systems with real-time and store-and-forward capabilities operating on a 128 kbit/s Internet connection. Participants were assessed pre- and post-treatment on acoustic measures of mean vocal sound pressure level, phonation time, maximum fundamental frequency range, and perceptual measures of voice, articulatory precision and speech intelligibility.\n Non-inferiority of the online LSVT® modality was confirmed for the primary outcome measure of mean change in sound pressure level on a monologue task. Additionally, non-significant main effects for the LSVT® environment, dysarthria severity, and interaction effects were obtained for all outcomes measures. Significant improvements following the LSVT® were also noted on the majority of measures. The LSVT® was successfully delivered online, although some networking difficulties were encountered on a few occasions. High participant satisfaction was reported overall.\n Online treatment for hypokinetic dysarthria associated with Parkinson's disease appears to be clinically valid and reliable. Suggestions for future research are outlined.\n © 2010 Royal College of Speech & Language Therapists.", "A review is undertaken of recent experimental studies of the effects of speech therapy offered to patients with Parkinson's disease. In contrast to earlier opinions based upon clinical impressions, the results of these studies indicate that the immediate gains from therapy measured within the clinical setting are readily detected, that these are perceived by patient's relatives and that there is reasonable evidence that benefits persist for some period after treatment. A further study is reported which tests the effects of a less intensive treatment regimen. This also gave positive results. Although questions remain regarding the most efficient form of treatment and the extent of its benefits outside the clinic, the existing results warrant greater optimism about the benefits of speech therapy offered to patients with Parkinson's disease.", "Twenty-six patients with the speech disorder of Parkinson's disease received daily speech therapy (prosodic exercises) at home for 2 to 3 weeks. There were significant improvements in speech as assessed by scores for prosodic abnormality and intelligibility' and these were maintained in part for up to 3 months. The degree of improvement was clinically and psychologically important, and relatives commented on the social benefits. The use of a visual reinforcement device produced limited benefit over and above that from prosodic exercises alone, except to patients with severe speech disorder.", "This study assessed the impact of the Lee Silverman Voice Treatment (LSVT) on vocal loudness [sound pressure level (SPL)] in a group of dysarthric individuals with idiopathic Parkinson's disease (IPD). Pre- to post-treatment changes in SPL in the treated group were compared with changes in voice SPL during the same time in two control groups: individuals with IPD not treated with the LSVT and in non-disordered individuals, age-matched to the patients. All subjects produced the same voice and speech tasks--sustaining vowel phonation, reading the \"Rainbow Passage,\" producing a short monologue, and describing a picture. These tasks were recorded at three different occasions: just prior to treatment, just after treatment, and 6 months following treatment. The individuals treated with LSVT increased voice SPL from baseline to post-treatment by an average of 8 dB and from baseline to 6 months follow-up by an average of 6 dB. These changes were statistically significant and perceptibly audible. No significant changes in SPL were observed in the control groups during the time corresponding to the treatment and follow-up. Differences in SPL between the treated and untreated patients at post-treatment and follow-up were statistically significant for all voice and speech tasks. These findings, along with others, provide additional support for the efficacy of the LSVT.", "This study examined the efficacy of a treatment, Oral Reading for Language in Aphasia (ORLA), delivered by computer to individuals with chronic nonfluent aphasia and compared its efficacy with the same treatment delivered by a speech-language pathologist (SLP).\n With ORLA, the person with aphasia systematically and repeatedly reads aloud sentences, first in unison and then independently. Following a no-treatment period, 25 individuals with chronic nonfluent aphasia were randomly assigned to receive 24 sessions of ORLA, 1-3 times per week, either by computer or by the SLP.\n For participants receiving computer ORLA, change made on the Western Aphasia Battery Aphasia Quotient (WAB-AQ) during the treatment phase was larger than the change made during the no-treatment phase. Positive effect sizes for change during treatment compared with change during the no-treatment phase were obtained and were benchmarked as medium or large for the WAB-AQ and discourse measures. There was no significant difference between outcomes for computer ORLA compared with SLP-ORLA.\n Low-intensity ORLA, delivered by computer to individuals with chronic nonfluent aphasia, is efficacious and may be equivalent to ORLA delivered by an SLP.", "Aphasic stroke patients were randomly allocated to either a speech therapy group receiving treatment twice a week for 24 weeks or a no-treatment control group. Patients in both groups improved and there were no significant differences in language recovery between the 104 patients allocated to the treatment group and the 87 allocated to the no-treatment group. This treatment regimen, which is representative of clinical practice, is ineffective for most aphasic stroke patients." ]

[ "17318618", "9269267", "10908688", "16331769", "1954640", "1375648", "1985618", "11203735", "9310109" ]

[ "Choosing between NSAID and arnica for topical treatment of hand osteoarthritis in a randomised, double-blind study.", "Copper-salicylate gel for pain relief in osteoarthritis: a randomised controlled trial.", "A randomized controlled trial comparing topical piroxicam gel with a homeopathic gel in osteoarthritis of the knee.", "Efficacy of topical diclofenac diethylamine gel in osteoarthritis of the knee.", "Treatment of arthritis with topical capsaicin: a double-blind trial.", "Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands.", "Corticosteroid injections in adhesive capsulitis: investigation of their value and site.", "Topical application of capsaicin for the treatment of localized pain in the temporomandibular joint area.", "Local NSAID gel (eltenac) in the treatment of osteoarthritis of the knee. A double blind study comparing eltenac with oral diclofenac and placebo gel." ]

[ "The use of topical preparations for symptom relief is common in osteoarthritis. The effects of ibuprofen (5%) and arnica (50 g tincture/100 g, DER 1:20), as gel preparations in patients with radiologically confirmed and symptomatically active osteoarthritis of interphalangeal joints of hands, were evaluated in a randomised, double-blind study in 204 patients, to ascertain differences in pain relief and hand function after 21 days' treatment. Diagnosis was according to established criteria; primary endpoints were pain intensity and hand function; statistical design was as per current regulatory guidelines for testing topical preparations. There were no differences between the two groups in pain and hand function improvements, or in any secondary end points evaluated. Adverse events were reported by six patients (6.1%) on ibuprofen and by five patients (4.8%) on arnica. Our results confirm that this preparation of arnica is not inferior to ibuprofen when treating osteoarthritis of hands.", "To assess the efficacy and safety of a copper-salicylate gel in osteoarthritis of the hip and knee.\n Randomised, double-blind, placebo-controlled study.\n Rheumatology Clinic of St Vincent's Hospital, Sydney, New South Wales (a tertiary referral hospital), June 1993 to October 1994.\n 116 patients with pain associated with osteoarthritis of the hip and/or knee (diagnosed by criteria of the European League against Rheumatism), drawn from patients attending the Clinic or self-referred after newspaper advertisements.\n Copper-salicylate or placebo gel (1.5 g) applied twice daily to the forearm for four weeks.\n Self-assessment of pain before the trial and after two and four weeks of treatment; patient and investigator assessments of efficacy; additional analgesia required; adverse reactions; and withdrawal rates.\n Pain scores at rest and on movement decreased in both the copper-salicylate and placebo groups by 13%-20%. There was no significant difference between the two groups for decrease in pain score, patient and investigator efficacy ratings, number of patients requiring paracetamol for extra analgesia (active, 77%; placebo, 71%) and average dose of paracetamol (active, 555 mg/day; placebo, 600 mg/day). Significantly more patients in the copper-salicylate group reported adverse reactions (83% versus 52% of the placebo group), most commonly skin reactions, and withdrew from the trial because of these reactions (17% versus 1.7% of the placebo group).\n Copper-salicylate gel applied to the forearm was no better than placebo gel as pain relief for patients with osteoarthritis of the hip or knee, but produced significantly more skin rashes.", ": To evaluate the efficacy and safety of a homeopathic gel vs an NSAID (piroxicam) gel in the treatment of osteoarthritis of the knee.\n : One hundred and eighty-four out-patients with radiographically confirmed symptomatic osteoarthritis of the knee were entered into a pragmatic, randomized, double-blind controlled trial and treated with 1 g of gel three times daily for 4 weeks. Main outcome measures were pain on walking as a Visual Analogue Score (VAS) and a single-joint Ritchie index.\n : One hundred and seventy-two of the 184 enrolled patients had endpoints for the main outcome parameters. The pain reduction was 16.5 mm VAS in the homeopathy group (n = 86) and 8.1 mm in the piroxicam group (n = 86); the difference between treatment groups was 8.4 mm (95% confidence interval 0.8-15.9), and after adjustment for pain at baseline it was 6.8 mm (95% confidence interval -0.3 to 13.8). There was no significant difference between treatment groups in the single-joint Ritchie index (P = 0.78). Adverse events occurred in 28 patients (12 homeopathy group, 5 withdrawn; 16 piroxicam group, 9 withdrawn); 18 of the events involved a local reaction (7 homeopathy group, 2 withdrawn; 11 piroxicam group, 5 withdrawn).\n : The homeopathic gel was at least as effective and as well tolerated as the NSAID gel. The presence of a clinically relevant difference between treatment groups cannot be excluded. The homeopathic gel supplemented by simple analgesics if required may provide a useful treatment option for patients with osteoarthritis.", "To assess the efficacy and safety of topical diclofenac diethylamine gel, 1.16%, 4 g applied qid for 3 weeks to relieve the symptoms of osteoarthritis (OA) of the knee.\n Patients with OA of the knee washed out their OA medications for at least 5 drug half-lives. Patients with adequately high baseline pain scores were randomized to apply either double-blind active or placebo gel for 3 weeks. Acetaminophen (up to 2 g/day) was supplied as rescue medication. In a diary, patients recorded compliance to dosing and use of rescue medication and assessed daily pain on movement, spontaneous pain, and pain relief. At weekly site visits, patients completed the Western Ontario and McMaster (WOMAC) Osteoarthritis Index Questionnaire, which includes assessment of pain, stiffness, and physical function, and assessed pain intensity \"right now.\" At the final visit, a global assessment of treatment efficacy was completed.\n Of 238 randomized patients, 237 were included in the intent to treat efficacy analysis. Treatments differed significantly for daily pain on movement at Day 5, and continued on most days through end of study. Peak differences were achieved in the second week. On the primary outcome, average pain on movement over Days 1-14, diclofenac gel was significantly superior to placebo gel. Scores for all 3 WOMAC indices for diclofenac gel treatment were significantly superior to placebo at Weeks 2 and 3. A significant difference was achieved on pain intensity \"right now\" at all 3 weeks. At the end of the study, patients rated diclofenac gel as significantly more effective in treating the pain of OA of the knee (p = 0.03) compared to placebo. There were no safety issues concerning adverse events or laboratory values.\n Diclofenac gel was effective and safe for relief of symptoms of OA of the knee over 3 weeks of dosing.", "The neuropeptide substance P has been implicated in the pathogenesis of inflammation and pain in arthritis. In this double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA) received capsaicin (a substance P depletor) or placebo for four weeks. The patients were instructed to apply 0.025% capsaicin cream or its vehicle (placebo) to painful knees four times daily. Pain relief was assessed using visual analog scales for pain and relief, a categorical pain scale, and physicians' global evaluations. Most of the patients continued to receive concomitant arthritis medications. Significantly more relief of pain was reported by the capsaicin-treated patients than the placebo patients throughout the study; after four weeks of capsaicin treatment, RA and OA patients demonstrated mean reductions in pain of 57% and 33%, respectively. These reductions in pain were statistically significant compared with those reported with placebo (P = 0.003 and P = 0.033, respectively). According to the global evaluations, 80% of the capsaicin-treated patients experienced a reduction in pain after two weeks of treatment. Transient burning was felt at the sites of drug application by 23 of the 52 capsaicin-treated patients; two patients withdrew from treatment because of this side effect. It is concluded that capsaicin cream is a safe and effective treatment for arthritis.", "Topical capsaicin 0.075% was evaluated for the treatment of the painful joints of rheumatoid arthritis (RA) and osteoarthritis (OA) in a 4 week double blind, placebo controlled randomized trial. Twenty-one patients were selected, all of whom had either RA (n = 7) or OA (n = 14) with painful involvement of the hands. Assessments of pain (visual analog scale), functional capacity, morning stiffness, grip strength, joint swelling and tenderness (dolorimeter) were performed before randomization. Treatment was applied to each painful hand joint 4 times daily with reassessment at 1, 2 and 4 weeks after entry. One subject did not complete the study. Capsaicin reduced tenderness (p less than 0.02) and pain (p less than 0.02) associated with OA, but not RA as compared with placebo. A local burning sensation was the only adverse effect noted. These findings suggest that topical capsaicin is a safe and potentially useful drug for the treatment of painful OA of the hands.", "Forty-eight patients with frozen shoulder for less than six months were assigned at random to receive three shoulder injections into the subacromial bursa or glenohumeral joint at weekly intervals. The treatment groups were (1) intra-articular methylprednisolone and lidocaine, (2) intrabursal methylprednisolone and lidocaine, (3) intra-articular lidocaine, (4) intrabursal lidocaine. The same physical therapy program was carried out for all patients. Assessments of pain and range of motion were performed by a physical therapist who was uninformed about the nature of the injection therapy. There was no significant difference in outcome between intrabursal injection and intra-articular injection. Injection of steroid with lidocaine had no advantage over lidocaine alone in restoring shoulder motion, but partial, transient pain relief occurred in two thirds of the steroid-treated patients.", "To determine the effectiveness of topical capsaicin cream application on localized pain in the temporomandibular joint (TMJ) area.\n A randomized, double-blind, placebo-controlled study was conducted on 30 patients suffering from unilateral pain in the TMJ area. Patients were randomly divided into experimental and placebo groups; they were instructed to apply 0.025% capsaicin cream or its vehicle to the painful TMJ area 4 times daily for 4 weeks. Subjective parameters of present pain, most severe pain, effect of pain on daily activities, and pain relief were assessed each week on a visual analog scale. Muscle and joint sensitivity to palpation on the painful and contralateral joints and maximal mouth opening (assisted/passive and non-assisted/active) were examined weekly by the same experienced examiner.\n Capsaicin cream produced no statistically significant influence on measured variables when compared to placebo. Both experimental and placebo groups showed statistically significant improvement in most variables during the experiment.\n The factor of time had a major effect in the non-specific improvement of the parameters assessed. The placebo effect played an important role in the treatment of patients with pain in the TMJ area.", "In a randomized, double blind, multicentre study with 4 weeks follow-up of 290 patients with osteoarthritis of the knee joint, a topical NSAID (eltenac) was compared with oral diclofenac and placebo. The main outcome, Lequesne's Index and pain by VAS showed no statistically significant differences between neither of the active treatments and placebo for the total study population. However, in patients with more severe symptoms, both active groups showed statistically significant differences to placebo. No severe adverse drug reactions were seen but the number of GI reactions were three times higher in the diclofenac group compared to the topical treatment. Local skin reactions were twice as frequent in the eltenac than in the placebo group. Taking into account the nature of the treatment for a chronic disease like OA, our results indicate that eltenac gel could be a safe alternative to oral NSAIDs." ]

[ "7778840", "9220235", "6378236", "9224082", "7767151", "6359995", "6313595", "15512809", "3006228" ]

[ "Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group.", "Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis.", "Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial.", "Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study.", "Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial.", "Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study.", "Oral acyclovir prophylactic treatment of herpes simplex infection after bone marrow transplantation.", "Oral valacyclovir as prophylaxis against herpes simplex virus reactivation during high dose chemotherapy for leukemia.", "Acyclovir prophylaxis in bone marrow transplant recipients." ]

[ "To document the effects of treatment with famciclovir on the acute signs and symptoms of herpes zoster and postherpetic neuralgia.\n A randomized, double-blind, placebo-controlled, multicenter trial.\n 36 centers in the United States, Canada, and Australia.\n 419 immunocompetent adults with uncomplicated herpes zoster.\n Patients were assigned within 72 hours of rash onset to famciclovir, 500 mg; famciclovir, 750 mg; or placebo, three times daily for 7 days.\n Lesions were assessed daily for as long as 14 days until full crusting occurred and then weekly until the lesions healed. Viral cultures were obtained daily while vesicles were present. Pain was assessed at each of the visits at which lesions were examined and then monthly for 5 months after the lesions healed. Safety was assessed throughout the study.\n Famciclovir was well tolerated, with a safety profile similar to that of placebo. Famciclovir accelerated lesion healing and reduced the duration of viral shedding. Most importantly, famciclovir recipients had faster resolution of postherpetic neuralgia (approximately twofold faster) than placebo recipients; differences between the placebo group and both the 500-mg famciclovir group (hazard ratio, 1.7 [95% CI, 1.1 to 2.7]) and the 750-mg famciclovir group (hazard ratio, 1.9 [CI, 1.2 to 2.9]) were statistically significant (P = 0.02 and 0.01, respectively). The median duration of postherpetic neuralgia was reduced by approximately 2 months.\n Oral famciclovir, 500 mg or 750 mg three times daily for 7 days, is an effective and well-tolerated therapy for herpes zoster that decreases the duration of the disease's most debilitating complication, postherpetic neuralgia.", "Ganciclovir is a broad-spectrum virustatic agent. Its efficacy and safety after ocular application have been demonstrated in studies of herpetic keratitis in rabbits. Two strengths of ganciclovir gel (0.05 and 0.15%) were compared with 3% acyclovir ointment in the treatment of superficial herpes simplex keratitis in humans.\n Two multicenter randomized clinical trials were carried out in Africa (Trial 1) and Europe (Trial 2). Sixty-seven patients (Trial 1) and 37 patients (Trial 2) from herpetic ulceration were recruited.\n The results showed no statistically significant difference between the treatment groups, although the healing rates tended to be better in the group receiving 0.15% ganciclovir gel, with healing rates of 85% (Trial 1) and 83% (Trial 2) as compared with 72% (Trial 1) and 71% (Trial 2) in the group receiving acyclovir ointment. Local tolerance was found to be superior with the gel formulation of ganciclovir with fewer complaints of discomfort (stinging, burning) or blurred vision after application of the drug. Systemic absorption of the drug was low. No hematologic changes were detected.\n These findings support the efficacy of ganciclovir gel in the treatment of ulcerative herpes simplex keratitis and demonstrate its superior local tolerance when compared with acyclovir ointment.", "Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200 mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P less than 0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P less than 0.001).", "To examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children.\n Randomised double blind placebo controlled study.\n Day care unit of a tertiary paediatric hospital.\n 72 children aged 1-6 years with clinical manifestations of gingivostomatitis lasting less than 72 hours; 61 children with cultures positive for herpes simplex virus finished the study.\n Duration of oral lesions, fever, eating and drinking difficulties, and viral shedding.\n Aciclovir suspension 15 mg/kg five times a day for seven days, or placebo.\n Children receiving aciclovir had oral lesions for a shorter period than children receiving placebo (median 4 v 10 days (difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier disappearance of the following signs and symptoms: fever (1 v 3 days (2 days, 0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days (3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to 4.9)). Viral shedding was significantly shorter in the group treated with aciclovir (1 v 5 days (4 days, 2.9 to 5.1)).\n Oral aciclovir treatment for herpetic gingivostomatitis, started within the first three days of onset, shortens the duration of all clinical manifestations and the infectivity of affected children. Further studies are needed to evaluate the ideal dose and length of treatment.", "To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers.\n Randomised, double blind, placebo controlled trial.\n 74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days.\n Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis.\n The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)).\n Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.", "Twenty-nine adult patients with acute leukemia receiving timed sequential chemotherapy participated in a randomized, double-blind, placebo-controlled trial of acyclovir prophylaxis against reactivated herpes simplex virus infection. Patients with pretreatment antibody titers of 1:16 or greater received acyclovir or placebo starting 4 days after their initial chemotherapy. Treatment was given either for 32 days or until the patients were discharged from the hospital or until a culture-positive herpes simplex virus infection was found. Culture-positive herpes simplex virus infection developed in 11 of 15 patients who received placebo. No infection appeared in 14 patients who received acyclovir (p less than 0.00005). No obvious acute drug toxicity was seen. Recurrent infection was seen in 6 of 14 patients after cessation of acyclovir when retreated with chemotherapy, suggesting no effect on viral latency in these 6 patients. Acyclovir provided highly effective prophylaxis against reactivated herpes simplex virus infections in adult patients with acute leukemia receiving timed sequential chemotherapy.", "In a double-blind controlled study, oral acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD); there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.", "Reactivation of herpes simplex virus is a common event in patients undergoing dose-intensive remission induction or consolidation chemotherapy of acute leukemia, for which either intravenous or oral acyclovir provides effective prophylaxis. This drug's short serum half-life and low oral bioavailability make frequent dosing necessary, however, and we therefore sought to determine if the pro-drug valacyclovir, which has improved bioavailability, could be successfully substituted for this indication. Eighty-one patients with leukemia were randomized to receive either 500 mg or 1,000 mg of valacyclovir orally every 8 h and followed clinically, as well as with serial surveillance cultures. Over a total of 1,979 days on study between the groups, and 380 throat cultures, no documented episodes of herpes simplex reactivation were noted. Valacyclovir was tolerated well with no evident drug-related toxicities. We conclude that valacyclovir at either of the two doses studied can be safely substituted for oral or intravenous acyclovir, and that it provides effective prophylaxis against reactivation of herpes simplex virus in this patient population.", "Forty-two patients undergoing bone marrow transplantation were included in a randomised, double-blind and placebo controlled trial of prolonged acyclovir prophylaxis against infections with viruses of the herpes group. Twenty patients were allocated to receive acyclovir and 22 to receive placebo. Acyclovir or placebo was administered i.v. at a dose of 250 mg/m2 twice daily, starting 5 days before transplantation. At 5 weeks after transplantation, administration was changed to tablets, 400 mg three times daily (children less than 6 years, 200 mg three times daily) and continued until 6 months after transplantation. In the placebo group, 10 acute herpes simplex virus (HSV) infections occurred in 7 patients (5 HSV-1 and 2 HSV-2), and another patient repeatedly shed HSV in throat washings. Five patients developed herpes zoster. Among patients receiving acyclovir only one episode of HSV infection occurred and no herpes zoster. The difference in the number of infection episodes and the number of infected patients was strongly significant (p = 0.0002 and 0.0017, respectively). The only acyclovir patient who reactivated HSV was terminally ill, and it is highly likely that she did not absorb a sufficient amount of the orally administered drug to control infection. All HSV and varicella zoster virus (VZV) infections were reactivations, and 9 of 10 patients who developed HSV infections or shed virus had a pre-transplantation HSV IgG titer of greater than 10 000 (ELISA). Acyclovir had no effect on cytomegalovirus (CMV), time of engraftment, or graft versus host disease (GVHD). Apart from a possible allergic reaction (skin rash) to acyclovir tablets, no adverse reactions were seen during this long prophylaxis with acyclovir." ]

[ "16912578", "17483124", "3307390", "8006396", "11386930", "8339411", "8938179", "19042837", "2530317" ]

[ "A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome).", "Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa.", "A prospective randomized clinical trial of peripheral amino acid-glucose supplementation in acute alcoholic hepatitis.", "Efficacy of steroid withdrawal and low-dose interferon treatment in chronic active hepatitis B. Results of a randomized multicenter trial. Swiss Association for the Study of the Liver.", "Enzyme replacement therapy in Fabry disease: a randomized controlled trial.", "Can further benefit be achieved by adding flosequinan to patients with congestive heart failure who remain symptomatic on diuretic, digoxin, and an angiotensin converting enzyme inhibitor? Results of the flosequinan-ACE inhibitor trial (FACET).", "Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure.", "A pilot phase II randomized, cross-over, double-blinded, controlled efficacy study of octreotide versus hyoscine hydrobromide for control of noisy breathing at the end-of-life.", "A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial." ]

[ "To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II.\n Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.5 mg/kg) infusions or every-other-week infusions of idursulfase (0.5 mg/kg). Efficacy was evaluated using a composite endpoint consisting of distance walked in 6 minutes and the percentage of predicted forced vital capacity based on the sum of the ranks of change from baseline.\n Patients in the weekly and every-other-week idursulfase groups exhibited significant improvement in the composite endpoint compared to placebo (P = 0.0049 for weekly and P = 0.0416 for every-other-week) after one year. The weekly dosing group experienced a 37-m increase in the 6-minute-walk distance (P = 0.013), a 2.7% increase in percentage of predicted forced vital capacity (P = 0.065), and a 160 mL increase in absolute forced vital capacity (P = 0.001) compared to placebo group at 53 weeks. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 46.9% of patients during the study.\n This study supports the use of weekly infusions of idursulfase in the treatment of mucopolysaccharidosis II.", "Anderson-Fabry disease is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb(3)) in the lysosomes of cells throughout the body that ultimately results in premature death from renal, cardiac or cerebrovascular complications. Until recently, there was no effective therapy available for this disease. The present study was designed to assess the safety and efficacy of enzyme replacement therapy with agalsidase alfa on the cardiac manifestations of Anderson-Fabry disease.\n The effects of therapy with agalsidase alfa on cardiac structure and function were assessed in a randomised, double-blind, placebo-controlled study of 15 adult male patients with Anderson-Fabry disease. The following parameters were measured at baseline and 6 months: left ventricular mass, QRS duration and levels of Gb(3) in cardiac tissue, urine sediment and plasma. After 6 months of the randomised trial patients were enrolled in a 2-year open-label extension study.\n Left ventricular mass, as measured by MRI, was significantly reduced following 6 months of treatment with agalsidase alfa compared with placebo (p = 0.041). A mean 20% reduction in myocardial Gb(3) content as assessed by serial transvenous endomyocardial biopsies was demonstrated over the 6 months of enzyme replacement compared to a mean 10% increase in patients receiving placebo (p = 0.42)\n Enzyme replacement therapy with agalsidase alfa resulted in regression of the hypertrophic cardiomyopathy associated with Anderson-Fabry disease.", "Twenty-eight patients with biopsy or clinical acute alcoholic hepatitis were prospectively randomized to 21 days of conventional therapy (14 control patients) or, in addition, to 2 L/day of a peripheral iv infusion of a 900 mosmol amino acid-glucose solution (14 patients). Cirrhosis was present in 64% of controls and in 54% of infused patients. There were three deaths in controls and one in the infused group. There were no significant intergroup differences in mortality, clinical findings, liver tests, or functional mass by the galactose elimination capacity either at entry or after completion of the study. In controls, there was intragroup improvement in serum bilirubin (p = 0.033) and AST (p = 0.008) but not in other \"liver tests\" or in functional hepatic mass by galactose elimination capacity. In infused patients there was improvement in bilirubin (p = 0.001), AST (p = 0.008), and serum albumin (p = 0.016). Improvement in functional mass by galactose elimination capacity was significant at the p = 0.052 level. Hyaline was initially present in six of eight pairs of biopsies in both groups. After treatment, five of six pairs in controls but only one of six pairs in the infused group still had hyaline (p = 0.03). This latter finding, if confirmed in larger groups, may be of considerable clinical importance. It is suggested that 3- to 4-wk trials of such protocols may require a longer duration of follow-up in greater numbers of patients to detect important advantages of amino acid-glucose infusions which are only implicit in these findings.", "Fifty-six patients with biopsy-proven, chronic active hepatitis B were included in a multi-center, randomized trial comparing steroid withdrawal followed by 1.5 MU recombinant interferon alpha 2b (Intron) with placebo withdrawal followed by either 1.5 or 5 MU interferon. The patients were equally distributed between the treatment groups with respect to biochemical and histologic activity as well as with respect to DNA levels and quantitative liver function tests. One patient was lost to follow up. After 1 year of treatment, 10/18, 13/19 and 11/18 patients had lost hepatitis B virus DNA in the three groups, respectively (non-significant). Transaminase levels were normal in 27/34 of the responders but in only 4/21 of the non-responders (p < 0.0001). Both galactose elimination capacity and aminopyrine breath test improved significantly in responders, but either did not change (aminopyrine breath test) or deteriorated in non-responders (galactose elimination capacity). Biopsy score improved in both groups but this reached statistical significance only in responders. This effect was due to improvements in both inflammatory and fibrotic activity. Side effects included almost universally a flu-like syndrome, granulocytopenia (1), depression (3) and thyroid dysfunction (2). Two deaths occurred, one due to hepatocellular cancer, and the other to hepatorenal syndrome after spontaneous bacterial peritonitis. A severe cytolytic episode was observed in three patients in the steroid withdrawal group. We conclude that in patients with marked histologic activity, lower doses of interferon may be as effective as the standard dose of 5 MU.(ABSTRACT TRUNCATED AT 250 WORDS)", "Fabry disease is a metabolic disorder without a specific treatment, caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). Most patients experience debilitating neuropathic pain and premature mortality because of renal failure, cardiovascular disease, or cerebrovascular disease.\n To evaluate the safety and efficacy of intravenous alpha-gal A for Fabry disease.\n Double-blind placebo-controlled trial conducted from December 1998 to August 1999 at the Clinical Research Center of the National Institutes of Health.\n Twenty-six hemizygous male patients, aged 18 years or older, with Fabry disease that was confirmed by alpha-gal A assay.\n A dosage of 0.2 mg/kg of alpha-gal A, administered intravenously every other week (12 doses total).\n Effect of therapy on neuropathic pain while without neuropathic pain medications measured by question 3 of the Brief Pain Inventory (BPI).\n Mean (SE) BPI neuropathic pain severity score declined from 6.2 (0.46) to 4.3 (0.73) in patients treated with alpha-gal A vs no significant change in the placebo group (P =.02). Pain-related quality of life declined from 3.2 (0.55) to 2.1 (0.56) for patients receiving alpha-gal A vs 4.8 (0.59) to 4.2 (0.74) for placebo (P =.05). In the kidney, glomeruli with mesangial widening decreased by a mean of 12.5% for patients receiving alpha-gal vs a 16.5% increase for placebo (P =.01). Mean inulin clearance decreased by 6.2 mL/min for patients receiving alpha-gal A vs 19.5 mL/min for placebo (P =.19). Mean creatinine clearance increased by 2.1 mL/min (0.4 mL/s) for patients receiving alpha-gal A vs a decrease of 16.1 mL/min (0.3 mL/s) for placebo (P =.02). In patients treated with alpha-gal A, there was an approximately 50% reduction in plasma glycosphingolipid levels, a significant improvement in cardiac conduction, and a significant increase in body weight.\n Intravenous infusions of alpha-gal A are safe and have widespread therapeutic efficacy in Fabry disease.", "Angiotensin converting enzyme inhibitors, diuretics, and digoxin are each effective in treating congestive heart failure, but many patients remain symptom-limited on all three medications. This trial was designed to determine whether the addition of oral flosequinan, a new direct-acting arterial and venous vasodilator with possible dose-dependent positive inotropic effects, improves exercise tolerance and quality of life in such patients.\n In a randomized, double-blind multicenter trial, 322 patients with predominantly New York Heart Association class II or III congestive heart failure and left ventricular ejection fractions of 35% or less, who were stabilized on a diuretic, angiotensin converting enzyme inhibitor, and digoxin, were treated with 100 mg flosequinan once daily, 75 mg flosequinan twice daily, or matching placebo. Efficacy was evaluated with serial measurements of treadmill exercise time, responses to the Minnesota Living With Heart Failure Questionnaire (LWHF), and clinical assessments during a baseline phase and a 16-week treatment period. After 16 weeks, 100 mg flosequinan once daily produced a significant increment in median exercise time (64 seconds at 16 weeks) compared with placebo (5 seconds), whereas the higher-dose flosequinan group did not show a statistically significant increase. Flosequinan (100 mg once daily) also improved the overall LWHF score significantly compared with placebo; both active therapies decreased the physical component, but 75 mg flosequinan twice daily was associated with a trend toward worsening of the emotional component. Most clinical assessments tended to improve on active therapy.\n These results indicate that additional symptomatic benefit can be attained by adding flosequinan to a therapeutic regimen already including a converting enzyme inhibitor. Because in the future most patients will fall into this category, flosequinan is a potential adjunctive agent in the management of severe congestive heart failure. However, because recent evidence indicates that the flosequinan dose studied in the present trial has an adverse effect on survival, the benefit-to-risk ratio must be assessed in individual patients.", "The objective of this pilot controlled study was to evaluate the extracorporeal liver assist device (ELAD) in patients with acute liver failure who were judged to still have a significant chance of survival (approximately 50%) and in those who had already fulfilled criteria for transplantation. Twenty-four patients were divided into two groups, 17 with a potentially recoverable lesion (group I) and 7 listed for transplantation (group II), and then randomly allocated to ELAD haemoperfusion or control. The median period of ELAD haemoperfusion was 72 hours (range 3-168 h). Biocompatibility of the device was good, with no acceleration in platelet consumption, and haemodynamic stability was maintained. Two patients were withdrawn from the study because of worsening of preexisting disseminated intravascular coagulation in one case and a hypersensitivity reaction in the other. Deterioration with respect to encephalopathy grade was more frequent in the control patients, 7 of 12 (58%), than in the ELAD-treated patients, 3 of 12 (25%). In group I where survival for the ELAD cases was 7 of 9 (78%), there was a higher than expected survival in the controls, 6 of 8 (75%). For group II cases, survival was 1 of 3 (33%) for the ELAD-treated patients, and 1 of 4 (25%) for the controls. Both of the survivors underwent transplantation. Assessment of additive function for the device revealed an improvement in galactose elimination capacity after 6 hours of haemoperfusion. Based on the results of this pilot-controlled trial, better indices of prognosis will be required, in addition to those used to select for transplantation, if patients at an earlier stage of clinical deterioration are to be included in future studies.", "Noisy breathing at the end of life (noisy breathing (\"NB\") occurs in up to 90% of people. Interventions have not been systematically evaluated. There has been clinical observation coupled with a proposed mechanism of effect that supports a role for octreotide in management of NB. The aim of this phase II study was to assess ten completed participants for the feasibility of an adequately powered phase III study. This randomized, double-blind, crossover pilot trial recruited participants from an inpatient palliative unit. Participants while well and their proxies simultaneously provided written informed consent. If NB were encountered, people were randomized to 200 mcg octreotide or 400 mcg hyoscine hydrobromide subcutaneously. If subsequent treatment was needed, the other medication was administered. A five point categorical scale documented the nurses' assessment of secretions over six hours. Eighty participants were consented of whom 10 (3 females, 7 males; median age 79, all with advanced cancer) received medication, five in each arm. There was no difference in the median time to administration of the second medication (3 hours). Two participants in each arm had a 2 category reduction of intensity after the second medication. Although feasible to consent and study this population in a way that respects autonomy and dignity even in the terminal hours of life, this pilot study suggests reconsideration of the pharmacological interventions (choice of agents, dosing, timing of dosing and pharmacokinetic profiles), standardizing of non-pharmacological care; and ways to measure directly family distress before further randomized studies for this symptom.", "In 1983, the Northern California Oncology Group (NCOG) instituted a randomized trial of intravenous (IV) versus intraarterial (IA) floxuridine (FUDR) administered via an implantable pump for patients with colorectal cancer metastatic to the liver. The study objectives were to compare the hepatic response rate, time to hepatic progression, and toxicity for the two treatment arms. The study design, which allowed patients failing IV FUDR to crossover to the IA arm, prevents a meaningful comparative analysis of survival. Patients with liver-only metastases (N = 143) were randomized, 76 to the IV arm and 67 to the IA arm, and 115 patients (65 IV, 50 IA) were fully evaluable. Of the 65 patients in the IV arm, 28 crossed over to IA treatment after failing IV FUDR. The dose-limiting toxicity of IV FUDR was diarrhea, whereas biliary toxicity limited both the dose and duration of IA FUDR therapy. Of the first 25 patients treated with IA FUDR at a dose of .3 mg/kg/day, 10 developed radiographically evident biliary strictures, and three developed permanent jaundice. With reduction of the initial IA FUDR dose to .2 mg/kg/day, and adoption of a policy of early dosage reduction, treatment interruption, or termination of therapy for persistent elevations in alkaline phosphatase, only two further cases of serious biliary toxicity occurred. However, 26 of the 50 IA FUDR patients ultimately had therapy terminated because of drug toxicity rather than disease progression. When compared with systemic infusion, infusion into the hepatic artery greatly enhanced the antitumor activity of FUDR against colorectal liver metastases. Although biliary toxicity is the most serious limitation of this form of therapy, biliary stricture and jaundice usually can be averted through careful monitoring of liver enzymes and early dosage reduction." ]

[ "2035325", "2587133", "1444522", "9875038", "7780540", "3421279", "16519625", "3601288", "1428134" ]

[ "Vitamin K to neonates. Peroral versus intramuscular administration.", "Maternal administration of vitamin K does not improve the coagulation profile of preterm infants.", "Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants.", "A new mixed micellar preparation for oral vitamin K prophylaxis: randomised controlled comparison with an intramuscular formulation in breast fed infants.", "[Efficacy of oral administration of a micellaar solution of vitamin K during the neonatal period].", "The use of antenatal vitamin K in the prevention of early neonatal intraventricular hemorrhage.", "Maternal antenatal administration of vitamin K1 results in increasing the activities of vitamin K-dependent coagulation factors in umbilical blood and in decreasing the incidence rate of periventricular-intraventricular hemorrhage in premature infants.", "Maternally administered antenatal vitamin K1: effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage.", "Comparative study of oral versus injectable vitamin K in neonates." ]

[ "In a randomized study of 300 infants, the effect of 1 mg of peroral vitamin K given at birth was compared to the same dose given as an intramuscular injection. The combined activity of coagulation factor II + VII + X taken after 48 and before 72 hours after delivery served as the primary endpoint. Prothrombin (antigen) and PIVKA II (acarboxyprothrombin) were also measured. All infants were observed for events of bleeding until discharge from the hospital, normally on the fifth day. No significant differences between the groups in any of the biochemical markers were observed. The 95% confidence limits of the differences were very narrow for all factors. No cases of bleeding were observed. We conclude that administration of 1 mg peroral vitamin K is as efficient as intramuscular administration of the same dose in the prevention of classical hemorrhagic disease of the newborn.", "The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants.", "A randomised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1, proteins induced by vitamin K absence (PIVKA-II), and clotting factors. Two groups of about 165 healthy breast fed infants who received at random 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age. Although vitamin K1 concentrations were statistically significantly higher in the intramuscular group, blood coagulability, activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups. At 2 weeks of age vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable. At 3 months vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5% of infants. Therefore, a repeated oral prophylaxis will be necessary to completely prevent (biochemical) vitamin K deficiency beyond the age of 1 month.", "To compare a new oral preparation of vitamin K1 (Konakion MM) containing lecithin and glycocholic acid with a standard intramuscular (IM) preparation during the first 8 weeks of life in exclusively breast fed infants.\n Infants were randomised at birth to the IM group (1 mg vitamin K) or the oral group (2 mg given at birth and repeated at 7 and 30 days of life). Prothrombin time (INR), plasma vitamin K1, and PIVKA II (undercarboxylated prothrombin) were monitored at 14, 30, and 56 days of age.\n Seventy nine infants were randomised to the oral group and 77 to the IM group. Sixty seven infants in each group completed eight weeks of the study. Prothrombin times did not differ between the two groups. Mean (SD) plasma vitamin K1 values (in ng/ml) decreased in both groups over time, but were higher in the oral group at 14 and 56 days: 2.0 (1.6) v 1.3 (1.1) at 14 days; 0.5 (0.3) v 0.5 (0.7) at 30 days; and 0.5 (0.8) v 0.2 (0.2) at 56 days of life. PIVKA II was raised (> or = 0.1 AU/ml) in cord blood in 47% of the infants. By 14 days, only one infant in each group had a raised PIVKA II value and both of these initially had high concentrations of PIVKA II in cord blood. At 30 days, there were no raised PIVKA II values. At 56 days, there were no raised PIVKA II values in the oral group, although three infants in the IM group had raised values.\n Plasma vitamin K concentrations were at least equal or significantly higher in babies given oral vitamin K supplements compared with IM treated babies at the time points measured. Through the first 8 weeks of life, multiple doses of the new oral preparation maintain haemostasis and vitamin K status in breast fed infants at least equal to that of the intramuscular preparation.", "Oral administration of vitamin K to neonates is quite satisfactory for preventing hemorrhagic disease of the newborn. The aim of this study is to test efficacy of a micellar solution of vitamin K at birth.\n Thirty full term infants, exclusively breast-fed during the first month of life, were included in this study. Seven of them (control group Cos) were given oral supplementation with 5 mg vitamin K1, cremophor; 15 other infants were given oral supplementation with 3 mg micellar solution of vitamin K1 (group MMos) and 7 were given an intramuscular injection of 1.5 mg micellar solution of vitamin K1 (group MMim). Prothrombin time activity and plasma vitamin K concentration were measured in the cord blood, 24 +/- 12 hours and 1 month after supplementation.\n No hemorrhage was seen and tolerance to vitamin K was good in the 3 groups. Mean prothrombin time activity was 54% in the cord blood, around 55% and 75%, 24 hrs and 1 month after supplementation, respectively; only one infant had low value (41%) by 1 month despite normal plasma vitamin K concentration. Two infants had low plasma vitamin K1 concentration by the second control despite normal prothrombin time activity; one belonged to the MMos group and the other to the Cos group. Mean values of plasma vitamin K1 concentration were higher by 1 month in the MMos group.\n A unique dose of micellar solution of vitamin K given orally at birth seems effective to prevent hemorrhagic disease.", "To establish the effect of antenatal vitamin K on the incidence and severity of intraventricular hemorrhage, 92 patients destined to deliver infants less than 32 weeks' gestation were, in a prospective fashion, randomly assigned to two groups. Group I received 10 mg of vitamin K1 intramuscularly every 5 days until delivery. Group II received no antenatal vitamin K1 therapy. There were 100 neonates less than 1500 gm, equally divided between groups I and II with respect to gestational age, birth weight, race, sex, presentation, route of delivery, duration of labor, Apgar scores, and arterial umbilical cord acid-base balance. The antenatal use of vitamin K resulted in significant reduction in the prothrombin time (12.7 versus 15.2 seconds) and partial thromboplastin time (42.6 versus 58.9 seconds; p less than 0.05). Furthermore, group I experienced a lower incidence of total (16% versus 36%) and severe (0% versus 11%) grades of intraventricular hemorrhage (p less than 0.05). This study suggests that the antenatal use of vitamin K may result in a reduction and severity of intraventricular hemorrhage in the neonate less than 1500 gm.", "Infants less than 35 weeks' gestation age are susceptible to periventricular-intraventricular hemorrhage (PIVH). This may be partially attributable to low concentrations of vitamin K-dependent coagulation factors. The purposes of this study were: (1) to determine the umbilical blood activity levels of vitamin K-dependent coagulation factors II, VII, IX and X; (2) to investigate the change in activities of these factors in premature infants' umbilical blood after prenatal administration of vitamin K1 to the mothers; and (3) to study the prophylactic effects on PIVH after maternal antenatal supplemental vitamin K1.\n Pregnant women in preterm labor at less than 35 weeks of gestation were randomly selected to receive antenatal vitamin K1 10 mg per day injection intramuscularly or intravenously for 2-7 days (vitamin K1 group, n = 40), or no such treatment (control group, n = 50). At the same period, cord blood samples were collected from thirty full-term neonates to compare the factor levels with those of premature infants. Intracranial ultrasound was performed by the same sonographer to determine the presence and severity of PIVH.\n The activities of vitamin K-dependent coagulation factors in umbilical blood in the control group were: factor II 25.64+/-9.49%, factor VII 59.00+/-17.66%, factor IX 24.67+/-8.88%, and factor X 30.16+/-5.02%. In full-term infants, the respective values were: factor II 36.70+/-4.88%, factor VII 64.54+/-10.62%, factor IX 30.18+/-5.69%, and factor X 34.32+/-12.63%. In vitamin K1 group these factors were: factor II 36.35+/-6.88%, factor VII 69.59+/-16.55%, factor IX 25.71+/-10.88%, and factor X 39.26+/-8.02%. The data suggest the absence of vitamin K-dependent coagulation factors in preterm infants, and antenatal supplement of vitamin K1 may increase the cord blood activity of factor II, VII and factor X (P < 0.001). In addition, the overall rates of PIVH in the vitamin K1 group and in controls were 32.4 and 52.0%, respectively (P = 0.036), and the frequency of severe PIVH was 5.0 and 20.0%, respectively (P = 0.038).\n Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation age may result in improved coagulation and may reduce the incidence as well as the severity degree of PIVH.", "Infants weighing 1500 g or less at birth are susceptible to intraventricular hemorrhage. This may be due in part to low concentrations of vitamin K-dependent clotting factors. Women in labor between 24-34 weeks' gestation were selected, according to their hospital registration number, to receive 10 mg vitamin K1 intramuscularly at least four hours before delivery. Control women received no vitamin K. The study included only infants born of mothers who were in hospital more than four hours before delivery, who weighed 1500 g or less at birth, and were less than 34 weeks' gestation. Twenty vitamin K1 and 33 control infants qualified for the study. Infants in both groups received routine postnatal vitamin K1. On admission, the infant's prothrombin activity and partial thromboplastin time (PTT) were measured. A head ultrasound was done between days 2 and 4 of life. Results demonstrated significantly improved prothrombin activity, a nonsignificant trend toward improved PTT, and a significantly decreased frequency of intraventricular hemorrhage in infants whose mothers had received vitamin K1. The effect of antenatal vitamin K1 on prothrombin activity and PTT appeared to be more pronounced in female infants.", "One hundred term exclusively breast fed babies weighing more than 2.5 kg were evaluated to determine the efficacy of various modes and doses of Vitamin K to prevent hemorrhagic disease of newborn (HDN). The babies were grouped into four categories of 25 each: Group A--1 mg Vitamin K intramuscular (Menadione sodium disulphite) at birth; Group B--0.5 mg Vitamin K intramuscular; Group C--1 mg Vitamin K orally, and group D--no Vitamin K. The prothrombin index was estimated in all babies between 36-72 hours of age. The results revealed a prothrombin index in Groups A, B, C and D as 94.98 +/- 7.64%, 95.08 +/- 9.91%, 92.51 +/- 10.10% and 80.39 +/- 15.90%, respectively. The differences between Groups A, B and C were insignificant. However, Group D, prothrombin index was significantly reduced as compared with the other three groups. It is, therefore, concluded that oral Vitamin K is as effective as injectable Vitamin K and its usage is recommended in our country to reduce complications and costs of parenteral therapy." ]

[ "17134849", "9803702", "18164144", "17347121", "20545388", "8122955", "12757964", "12873248", "3276670" ]

[ "Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence: two double-blind, randomized, clinical trials.", "Superior efficacy of cognitive-behavioral therapy for urban crack cocaine abusers: main and matching effects.", "Levodopa pharmacotherapy for cocaine dependence: choosing the optimal behavioral therapy platform.", "Preliminary feasibility and efficacy of a brief motivational intervention with psychophysiological feedback for cocaine abuse.", "Contingency management and levodopa-carbidopa for cocaine treatment: a comparison of three behavioral targets.", "Psychotherapy and pharmacotherapy for ambulatory cocaine abusers.", "A pilot trial of olanzapine for the treatment of cocaine dependence.", "Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence.", "Pharmacological and behavioral treatments of cocaine dependence: controlled studies." ]

[ "The role of dopamine in cocaine abuse has been long recognized. Cocaine use can profoundly alter dopaminergic functioning through depletion of this monoamine and changes in receptor functioning. Based on these facts, levodopa (L-dopa) pharmacotherapy may be helpful in reducing or abolishing cocaine use.\n The current studies sought to evaluate the safety, tolerability and efficacy of L-dopa as a treatment for cocaine dependence.\n In Study 1, 67 cocaine-dependent subjects were randomized in a 5-week, double-blind, placebo-controlled safety trial. Subjects received either placebo, or 400 mg L-dopa plus 100 mg of the peripheral decarboxylase inhibitor, carbidopa, in a sustained-release preparation (Sinemet CR). In Study 2, 122 cocaine-dependent subjects were enrolled in a 9-week, randomized, double-blind, placebo-controlled trial to compare placebo to 400/100 mg and 800/200 mg L-dopa/carbidopa treatments. Placebo or L-dopa were administered twice daily in both studies.\n L-dopa was well tolerated with similar retention and medication adherence rates compared to placebo. Only two side effects occurred more often in L-dopa-treated patients: nausea and dizziness. L-dopa lowered diastolic blood pressure in a dose-dependent fashion. In these trials, L-dopa had no effect on cocaine use, cocaine craving, or mood.\n These two studies demonstrate the safety and tolerability of L-dopa pharmacotherapy in cocaine-dependent patients. No evidence for greater efficacy of L-dopa compared to placebo was observed. The possibility of enhancing treatment effects by combining L-dopa with other behavioral or pharmacological interventions is discussed.", "This study evaluated the efficacy of cognitive-behavioral therapy (CBT) and 12-step facilitation (12SF) in treating cocaine abuse. Participants (N = 128) were randomly assigned to treatment conditions and assessed at baseline and at Weeks 4, 8, 12, and 26. Treatment lasted for 12 weeks. It was hypothesized that participants treated with CBT would be significantly more likely to achieve abstinence from cocaine than participants treated with 12SF. A series of patient-treatment matching hypotheses was also proposed. Across 2 different outcome variables, it was found that participants in CBT were significantly more likely to achieve abstinence than participants in 12SF. In addition, some support for matching hypotheses was found, suggesting that both psychotherapies may be differentially effective for identified subgroups of persons that abuse cocaine.", "The dopamine precursor levodopa has shown some, albeit relatively weak, promise in treating cocaine dependence. This study sought to identify the most appropriate behavioral therapy platform for levodopa pharmacotherapy by evaluating its effect when administered in combination with behavioral platforms of varying intensities.\n A total of 161 treatment-seeking cocaine dependent subjects received sustained release levodopa/carbidopa (400/100mg bid, Sinemet) or placebo delivered in combination with Clinical Management (ClinMan); ClinMan+cognitive behavioral therapy (CBT); or ClinMan+CBT+voucher-based reinforcement therapy (VBRT) in a 12-week randomized, placebo-controlled, double-blind (for medication condition) trial. Medication compliance was monitored with riboflavin (100mg/capsule) and the Medication Event Monitoring System. Protocol compliance was addressed in weekly, 10-min nurse-delivered ClinMan sessions. Weekly, 1-h CBT sessions focused on coping skills training. VBRT (with escalating reinforcer value) provided cash-valued vouchers contingent on cocaine-negative urine toxicology results. Urine benzoylecgonine assays collected thrice-weekly were analyzed by intention-to-treat criteria using generalized linear mixed models.\n Levodopa main effects were found on all outcome measures of cocaine use. Contrasts testing the levodopa-placebo difference within each behavioral platform found reliable effects, favoring levodopa, only in the VBRT platform. Levodopa treatment with vouchers produced higher proportions of cocaine-negative urines and longer periods of consecutive abstinence compared to other treatment combinations.\n This is the first study to find a significant treatment effect for levodopa and, in doing so, to demonstrate that the magnitude of this effect is dependent upon conditions of the behavioral therapy platform. The data support use of levodopa with abstinence-based reinforcement therapy as one efficacious combination in cocaine dependence disorder treatment.", "Motivational interviewing (MI) with personalized feedback, particularly related to biological markers of risk or harm, has been found effective for alcohol use disorders, but has not been fully investigated in cocaine use disorders. A randomized, controlled pilot study evaluating the feasibility and preliminary efficacy of a brief MI intervention using EEG/ERP graphical feedback for cocaine abusers was conducted. Treatment-seeking cocaine abusers (N = 31) were randomly assigned to a two-session MI intervention or a minimal control condition. All participants received EEG assessments at intake and post-treatment. Results indicated that the MI intervention was feasible and the subjective impact of the EEG feedback was positive. Significant group differences in percentage of cocaine positive urine screens across the study were found, favoring the MI group; 84.9% for the control group and 62.6% in the MI group, p < .05. Further research must determine the specific conditions under which MI is most appropriate and efficacious.", "New data support use of levodopa pharmacotherapy with behavioral contingency management (CM) as one efficacious combination in cocaine dependence disorder treatment. A potential mechanism of the combined treatment effects may be related to dopamine-induced enhancement of the saliency of contingently delivered reinforcers. Evidence to support this mechanism was sought by evaluating levodopa-enhancing effects across distinct CM conditions that varied in behavioral targets. A total of 136 treatment-seeking, cocaine dependent subjects participated in this 12-week, randomized, placebo-controlled trial of levodopa (vs. placebo) administered in combination with one of three behavioral CM conditions. In the CM-URINE condition, subjects received cash-valued vouchers contingent on cocaine-negative urine toxicology results. In the CM-ATTEND condition, the same voucher schedule was contingent on attending thrice weekly clinic visits. In the CM-MEDICATION condition, the same voucher schedule was contingent on Medication Event Monitoring Systems- and riboflavin-based evidence of pill-taking behavior. Primary outcomes associated with each CM target behavior were analyzed using generalized linear mixed models for repeated outcomes. CM responding in the CM-ATTEND and CM-MEDICATION conditions showed orderly effects, with each condition producing corresponding changes in targeted behaviors, regardless of medication condition. In contrast, CM responding in the CM-URINE condition was moderated by medication, with levodopa-treated subjects more likely to submit cocaine-negative urines. These findings specify the optimal target behavior for CM when used in combination with levodopa pharmacotherapy.", "At present, there is no consensus regarding effective treatment for cocaine abuse or the most productive roles for the two major forms of treatment, pharmacotherapy and psychotherapy. We conducted the first randomized clinical trial evaluating psychotherapy and pharmacotherapy, alone and in combination, as treatment for ambulatory cocaine abusers.\n One hundred thirty-nine subjects were assigned to one of four conditions offered over a 12-week abstinence initiation trial: relapse prevention plus desipramine hydrochloride, clinical management plus desipramine, relapse prevention plus placebo, and clinical management plus placebo. All treatments were manual-guided, delivered by experienced therapists, and monitored to promote the integrity of both forms of treatment.\n First, although all groups showed significant improvement, significant main effects for medication or psychotherapy, or their combination, were not found for treatment retention, reduction in cocaine use, or other outcomes at 12 weeks. Second, baseline severity of cocaine use interacted differently with psychotherapy and pharmacotherapy: higher-severity patients had significantly better outcome when treated with relapse prevention than with clinical management, while desipramine was associated with improved abstinence initiation among lower-severity subjects. Third, desipramine was significantly more effective than placebo in reducing cocaine use over 6, but not 12, weeks of treatment. Fourth, depressed subjects had greater reduction in cocaine use than nondepressed subjects and had better response to relapse prevention than to clinical management.\n These findings underscore the significance of heterogeneity among cocaine abusers and the need to develop specialized treatments for clinically distinct subgroups of cocaine abusers.", "Multiple lines of evidence suggest both dopaminergic and serotonergic involvement in the reinforcing effects of cocaine. Medications such as olanzapine, which block dopamine D2 receptors, as well as serotonin receptors 5HT2A and 5HT2C may be able to reduce cocaine use in cocaine dependent patients by reducing the euphoric effects of cocaine and attenuating cocaine craving.\n This was a 12-week, double blind, placebo controlled, pilot trial involving 30 cocaine dependent subjects. Subjects received either olanzapine (10 mg/day) or identical placebo. Outcome measures included treatment retention, qualitative urine benzoylecgonine tests, cocaine craving, clinical global impression scores, and results from the addiction severity index.\n Treatment retention was slightly, but significantly, better in the placebo-treated subjects. Placebo-treated subjects were more likely to be abstinent from cocaine during the trial compared to olanzapine-treated subjects, based on urine benzoylecgonine results. Olanzapine was not superior to placebo in any outcome measure.\n The results of this trial do not support the usefulness of olanzapine for the treatment of cocaine dependence. In fact, olanzapine may worsen cocaine treatment outcome.", "To establish the feasibility of conducting a placebo-controlled clinical trial of dexamphetamine replacement therapy for cocaine dependence and to obtain preliminary data.\n Double-blind randomized placebo-controlled trial.\n Thirty cocaine-dependent injecting drug users.\n Subjects were assigned randomly to receive 60 mg/day dexamphetamine (n = 16) or placebo (n = 14) for 14 weeks.\n Immunoassay and mass spectrometric techniques were used to identify cocaine metabolites in urine. Subjects were screened using the Composite International Diagnostic Interview and DSM-IV. The Opiate Treatment Index, Brief Symptom Inventory, Severity of Dependence Scale and visual analogue craving scales were used to collect pre- and post-self-report data.\n Treatment retention was equivalent between groups; however, outcomes favoured the treatment group with no improvements observed in the placebo control group. The proportion of cocaine-positive urine samples detected in the treatment group declined from 94% to 56% compared to no change in the placebo group (79% positive). While the improvements were not significant between groups, within-group analysis revealed that the treatment group reduced self-reported cocaine use (P = 0.02), reduced criminal activity (P = 0.04), reduced cravings (P < 0.01) and reduced severity of cocaine dependence (P < 0.01) with no within-group improvements found in the placebo group.\n A definitive evaluation of the utility of dexamphetamine in the management of cocaine dependence is feasible and warranted.", "The cocaine epidemic has stimulated novel treatments aimed at reducing relapse to this extremely addicting drug. After detoxification and standard treatment, former cocaine users continue to exhibit strong cocaine craving and physiological changes when presented with cocaine-related stimuli. Because these conditioned responses may increase the risk of relapse, a new treatment has been developed to extinguish such responses. The extinction process, consisting of repeated presentations of cocaine-related stimuli until the stimuli gradually lose their ability to evoke conditioned responses, is integrated into a comprehensive rehabilitation program. Cocaine dependence is often combined with opiate dependence. Desipramine has been added to methadone maintenance in an attempt to reduce dependence on both substances. Methadone impedes catabolism of desipramine so that relatively low doses of desipramine may produce antidepressant effects and possibly reduce the desire to use cocaine. Preliminary evidence from a placebo-controlled study of desipramine in combination with methadone suggests that desipramine produces significant improvements in psychological functioning, but its effects on reduction of cocaine use are less dramatic." ]

[ "10587936", "15282836", "17071020", "11258740", "9513628", "12084137", "7573630", "19705680", "9170765" ]

[ "Comparing the impact of standard and abbreviated treatment in a therapeutic community. Findings from the district of Columbia treatment initiative experiment.", "Modified TC for MICA offenders: crime outcomes.", "Adapting judicial supervision to the risk level of drug offenders: discharge and 6-month outcomes from a prospective matching study.", "Multisystemic treatment of substance-abusing and dependent delinquents: outcomes, treatment fidelity, and transportability.", "Increasing participation in substance abuse aftercare treatment.", "Process and outcome changes with relapse prevention versus 12-Step aftercare programs for substance abusers.", "The effectiveness of alternative planned durations of residential drug abuse treatment.", "Visual representation tools for improving addiction treatment outcomes.", "Reinforcing operants other than abstinence in drug abuse treatment: an effective alternative for reducing drug use." ]

[ "This study examines the efficacy of providing Enhanced Abbreviated or Standard Inpatient treatment and Outpatient treatment to drug-abusing clients. The experiment randomly assigned 412 clients to two therapeutic community programs, which differed primarily in planned duration. This study addressed limitations of prior research, as it used random assignment of clients to treatment programs, achieved high follow-up rates and used objective measures of drug use and criminal history. Self-reports and objective measures of criminal activity and substance abuse were collected at pre- and posttreatment interviews. Completing the entire 12-month program (inpatient and outpatient) was more important than duration of inpatient program attended. Regardless of program, completers had substantial reductions in posttreatment drug abuse and arrests. A 12-month course of treatment including at least 6 months in a therapeutic community followed by outpatient treatment can produce marked reductions in drug abuse and crime among persons who complete both phases.", "The study randomly assigned male inmates with co-occurring serious mental illness and chemical abuse (MICA) disorders to either modified therapeutic community (MTC) or mental health (MH) treatment programs. On their release from prison, MICA inmates who completed the prison MTC program could enter the MTC aftercare program. The results, obtained from an intent-to-treat analysis of all study entries, showed that inmates randomized into the MTC group had significantly lower rates of reincarceration compared with those in the MH group. The results also show that differences between the MTC + aftercare and comparison group across a variety of crime outcomes (i.e. any criminal activity, and alcohol or drug related criminal activity) are consistent and significant, and persist after an examination of various threats to validity (e.g. initial motivation, duration of treatment, exposure to risk). This study provides some support for the effectiveness of the prison TC only condition. The findings are encouraging and consonant with other studies of integrated prison and aftercare TC programs for substance abusing non-MICA offenders, although qualified by the possibility that selection bias (i.e. differences in motivation on entry into aftercare) may be operating. Nevertheless, given the available evidence and the need for effective programming for MICA offenders, program and policy makers should strongly consider developing integrated prison and aftercare modified TC programs for MICA offenders.\n Copyright 2004 John Wiley & Sons, Ltd.", "This article reports recent findings from a program of experimental research examining the effects of adapting judicial supervision to the risk level of drug-abusing offenders. Prior studies revealed that high-risk participants with (1) antisocial personality disorder or (2) a history of drug abuse treatment performed significantly better in drug court when they were scheduled to attend frequent, bi-weekly judicial status hearings in court. Low-risk participants performed equivalently regardless of the schedule of court hearings. The current study prospectively matched misdemeanor drug court clients to the optimal schedule of court hearings based upon an assessment of their risk status, and compared outcomes to those of clients randomly assigned to the standard schedule of court hearings. Results confirmed that high-risk participants graduated at a higher rate, provided more drug-negative urine specimens at 6 months post-admission, and reported significantly less drug use and alcohol intoxication at 6 months post-admission when they were matched to bi-weekly hearings as compared to the usual schedule of hearings. These findings yield practical information for enhancing the efficacy and cost-efficiency of drug court services. Directions for future research on adaptive programming for drug offenders are discussed.", "The effectiveness and transportability of multisystemic therapy (MST) were examined in a study that included 118 juvenile offenders meeting DSM-III-R criteria for substance abuse or dependence and their families. Participants were randomly assigned to receive MST versus usual community services. Outcome measures assessed drug use, criminal activity, and days in out-of-home placement at posttreatment (T2) and at a 6-month posttreatment follow-up (T3); also treatment adherence was examined from multiple perspectives (i.e., caregiver, youth, and therapist). MST reduced alcohol, marijuana, and other drug use at T2 and total days in out-of-home placement by 50% at T3. Reductions in criminal activity, however, were not as large as have been obtained previously for MST. Examination of treatment adherence measures suggests that the modest results of MST were due, at least in part, to difficulty in transporting this complex treatment model from the direct control of its developers. Increased emphasis on quality assurance mechanisms to enhance treatment fidelity may help overcome barriers to transportability.", "Increasing the length of participation in alcohol and drug treatment is associated with improved outcomes (1). The present study was designed to increase substance abuse aftercare participation following completion of inpatient treatment. We compared the effect of a 20-minute aftercare orientation session to a minimal treatment condition on aftercare group therapy participation. The orientation session was conducted by an aftercare group therapist, who met with the participant to encourage him to attend aftercare, to explain why aftercare is helpful, and to have him sign an aftercare participation contract. Participants in the minimal treatment condition watched a videotape on motivation to reach goals. Participants were 40 males in an inpatient substance abuse treatment program at a Veterans Affairs Medical Center (VAMC). Ninety percent were alcohol dependent; 35% were cocaine dependent; 10% were marijuana dependent; and 10% were polysubstance dependent. Participants who received the aftercare orientation were more likely to attend aftercare (70%) than those who received the minimal treatment (40%). Additionally, the former group attended more sessions (x = 3.0) than those who were not oriented to aftercare (x = 1.4). The utility and limitations of a brief orientation session on aftercare adherence are discussed.", "Presumptive support was sought for mechanisms of action whereby two conceptually distinct aftercare programs, relapse prevention (RP) and 12-Step facilitation (TSF), impact upon substance abusers.\n Adults who had just completed intensive treatment were assigned randomly to either RP (n=61) or TSF (n=70) aftercare programs.\n Three residential treatment facilities.\n Trained counselors delivered to small groups a manualized aftercare program which focused either upon the utilization of cognitive-behavioral processes to orchestrate change through an individualized treatment plan (i.e. RP) or which sought to facilitate utilization of AA's 12 Steps (i.e. TSF).\n Process measures developed specifically to quantify either: (a) the changes in self-efficacy process in RP or (b) the utilization of AA's principles in TSF, as well as psychosocial and substance abuse indices were administered to all patients pre- and post-aftercare and at 6-month follow-up.\n A significant relationship between changes in measures of self- efficacy for RP participants as well as a trend for a relationship between process-specific change for TSF participants partially satisfied the first condition for presumptive support. The fact that the intervention-specific mediators covaried with several outcome indices, and that removal of such mediators attenuated prediction of outcome met, respectively, the second and third conditions for presumptive support.\n Carefully orchestrated RP and TSF aftercare programs yield process changes that are related positively to improved outcome.", "Randomized controlled trials were conducted at two residential drug abuse treatment facilities to compare programs that differed in planned duration. One trial compared a 6-month and a 12-month therapeutic community program (n = 184), and the second compared a 3-month and a 6-month relapse prevention program (n = 444). Retention rates over comparable time periods differed minimally by planned treatment duration, and the longer programs had lower completion rates. There was no effect in either trial of planned treatment duration on changes in psychosocial variables between admission and exit or on rates or patterns of drug use at follow-up between 2 and 6 months after exit.", "To examine the effectiveness of two visual representation counseling techniques for reducing illicit drug use, participants were randomly assigned to receive standard treatment \"as usual\" or standard treatment supplemented with free mapping or free plus guide mapping. Each counselor delivered all types of treatment to participants to control for differences in counselor characteristics (e.g., experience, empathy). Eighty-two participants who had received one year of methadone maintenance treatment and had urinalysis and self-report data for illicit drug use six months after treatment were examined. Compared to participants receiving standard treatment, participants randomly assigned to the free plus guide mapping condition had significantly lower opiate use based on urinalysis and self-report data. These results support the use of the free plus guide visual representation strategy and provide evidence for the concurrent validity of self-report measures of illicit drug use.", "This study examines the effectiveness of using vouchers to reinforce either the provision of urine samples testing negative for illicit drugs (UA group) or the completion of objective, individually defined, treatment-plan-related tasks (TP group). A third group was assigned to the clinic's standard treatment (STD group). Participants were randomly assigned to groups after a 6-week baseline-stabilization period. Urine specimens were collected thrice weekly throughout the study. In the UA condition, participants earned $5 (U.S. dollars) in vouchers for each drug-free urine submitted. In the TP condition, participants earned up to $15 in vouchers per week for demonstrating completion of treatment plan tasks assigned by their counselors. Contingencies were in effect for 12 weeks, after which all participants received the clinic's standard treatment. Urinalysis results indicate that the TP intervention was significantly more effective in reducing illicit drug use than either the UA or STD interventions. These effects were maintained with a trend toward continuing improvement for the TP groups even after contingencies were discontinued." ]

[ "18260482", "7675718", "1527129", "2670950", "10791665", "7327728", "8245085", "3881447", "11886906" ]

[ "Conservative management of minimally displaced isolated fractures of the ulnar shaft.", "Treatment of ulnar shaft fractures: a prospective, randomized study.", "Isolated ulnar shaft fractures. Comparison of treatment by a functional brace and long-arm cast.", "Operative or conservative treatment for trochanteric fractures of the femur. A randomised epidemiological trial in elderly patients.", "Randomized prospective study of humeral shaft fracture fixation: intramedullary nails versus plates.", "The treatment of unstable intertrochanteric fractures of the hip: a prospective trial of 150 cases.", "Intra-articular fractures of the calcaneum treated operatively or conservatively. A prospective study.", "A prospective, randomized study of the management of severe ankle fractures.", "Treatment of reverse oblique and transverse intertrochanteric fractures with use of an intramedullary nail or a 95 degrees screw-plate: a prospective, randomized study." ]

[ "The purpose of this prospective study was to compare three different ways of conservative management of isolated fractures of the ulnar shaft: immediate mobilisation, below-elbow plaster cast and above-elbow plaster cast immobilisation. Over a 24-month period, 102 minimally displaced isolated fractures of the distal two-thirds of the ulnar shaft were treated on an outpatient basis. Thirty-two fractures were immobilised with an above-elbow plaster cast for 3 weeks and a below-elbow plaster cast for an additional 3 weeks. Thirty-six fractures were immobilised with a below-elbow plaster cast for 6 weeks. The remaining 34 fractures were managed with immediate mobilisation. Radiological healing, range of motion of the wrist, and pain were assessed. Results were good and were comparable in terms of healing, time to healing, pain and range of motion of the wrist.", "The treatment of isolated ulnar shaft fractures is controversial. Previous studies comparing treatment options have been largely retrospective and nonrandomized. In this study, consecutive patients were randomized into treatment groups of long arm plaster immobilization, short arm plaster immobilization, or Ace Wrap bandage, based on the order of hospital admission. Thirty-one patients were followed until radiographic or clinical union, with no significant difference in time to union between groups. Age, sex, fracture pattern, and displacement did not significantly influence time to union or final angulation. Two patients in both the long arm cast group and the short arm cast group lost significant motion at final follow up. Seventy percent of patients in the Ace Wrap group failed treatment secondary to pain and were converted to plaster immobilization. Furthermore, patients in this group demonstrated significantly greater angulation than those treated in a long arm cast. Our results demonstrate that above-elbow plaster immobilization offers no advantage over below-elbow immobilization. We recommend short arm casting for a period of 8 weeks.", "In a prospective study, we randomly allocated 39 patients with isolated fractures of the lower two-thirds of the ulnar shaft to treatment either by a prefabricated functional brace or a long-arm cast. Significantly better wrist function and a higher percentage of satisfied patients were found in the braced group. Thirteen patients returned to employment while still wearing the brace but only one was able to work in a cast.", "All elderly patients with extracapsular hip fractures seen in hospitals in Newcastle upon Tyne over a 12-month period were studied and followed up for six months. At one of the hospitals, patients were randomised to treatment by AO dynamic hip-screw or by traction. Complications specific to the two treatments were low, and general complications, six-month mortality and prevalence of pain, leg swelling and unhealed sores, showed no difference between the two modes of treatment. Operative treatment gave better anatomical results and a shorter hospital stay, but significantly more of the patients treated by traction showed loss of independence six months after injury.", "To compare the clinical and radiographic results for locked intramedullary (IM) nails and plates used in the treatment of humeral diaphyseal fractures.\n Prospective randomization by sealed-envelope technique of eighty-four patients into two study groups: those treated by intramedullary nailing (IMN group; n = 38) and those treated by compression plating (PLT group; n = 46).\n Patients admitted consecutively to a university-affiliated Level I trauma center. PATIENT/PARTICIPANTS: All skeletally mature patients admitted to Harborview Medical Center with acute humeral shaft fractures requiring surgical stabilization. Fractures of the diaphysis were defined as being at least three centimeters distal to the surgical neck and at least five centimeters proximal to the olecranon fossa.\n Treatment with locking antegrade intramedullary humeral nails (Russell-Taylor design [Smith and Nephew Richards]) or with 4.5-millimeter dynamic compression and limited contact dynamic compression plates (AO design [Synthes]).\n Clinical outcome measurements included fracture healing, radial nerve recovery, infection, and elbow and shoulder discomfort. Radiographic measurements included fracture alignment, time to healing, delayed union, and nonunion.\n Follow-up averaged thirteen months. Forty-two fractures (93 percent) in the PLT group were healed by sixteen weeks versus thirty-three fractures (87 percent) in the IMN group (p = 0.70). Shoulder pain and a decrement in shoulder range of motion (ROM) were significant associations with IMN (p = 0.007 for both variables) but not with PLT. A decrement in elbow ROM was significantly associated with PLT (p = 0.03), especially for fractures of the distal third of the diaphysis, whereas elbow pain was not (p = 0.123). The sum of other complications demonstrated nearly equal prevalence for both treatment groups.\n For patients requiring surgical treatment of a humeral shaft fracture, intramedullary nailing and compression plating both provide predictable methods for achieving fracture stabilization and ultimate healing.", "We report a prospective clinical trial of 150 cases for the treatment of unstable intertrochanteric fracture of the neck of the femur. Three methods were tested in our series--skeletal traction with a tibial pin, medial displacement osteotomy and valgus osteotomy--with 50 patients in each group. Our results showed no significant difference between those treated with the Dimon and Hughston osteotomy and those treated by the Sarmiento osteotomy. Conservative treatment of skeletal traction for unstable fracture was found to be well tolerated by the Chinese patient. A low mortality and morbidity rate was found in this series with an overall infection rate of 4 per cent.", "We report a prospective trial of 66 patients with intraarticular fractures of the calcaneum. All fractures were assessed by CT. Patients with displaced fractures were randomised to receive either conservative (n = 31) or operative treatment (n = 25). Undisplaced fractures (n = 10) were treated conservatively. Operation involved open reduction of the posterior subtalar joint, and fixation with Kirschner wires. All 66 patients were reviewed at a minimum of one year (mean 23 months). After conservative treatment the undisplaced fractures had slightly better results than the displaced fractures. There was no significant difference in outcome between the operatively and the conservatively treated displaced fractures. We have also documented prospectively the natural history of the injury, which is of use in assessing prognosis for both clinical and medicolegal purposes.", "One hundred and thirty-eight patients with a closed grade-4 supination-external rotation or pronation-external rotation ankle fracture (Lauge-Hansen classification) who were seen in the emergency room of the University of Chicago Hospitals were entered into a randomized study of the results of various methods of treatment. Ninety-six patients with satisfactory initial closed reduction were randomized between continued closed treatment in a plaster cast and open reduction with rigid internal fixation according to the techniques of the Association for the Study of Internal Fixation (ASIF). Forty-two patients with unsatisfactory closed reduction were randomized between open reduction with internal fixation of only the medial malleolus and open reduction with rigid internal fixation according to the ASIF techniques. Of the 138 patients who were admitted to the study, only seventy-one (51 per cent) could be followed for an average of 3.5 years (a typical return rate of urban trauma centers). The outcomes were evaluated by a scoring system that included clinical, anatomical, and arthritis scores. Statistical analysis of the data showed that, of the patients with initial satisfactory closed reduction, the ones treated by open reduction and rigid internal fixation had significantly higher total scores, particularly the patients who were more than fifty years old and those with a medial malleolar fracture. The small number of patients with unsatisfactory closed reduction who were treated by one of the two types of open reduction and internal fixation and were available for follow-up precluded drawing any conclusions about the superiority of one method of internal fixation over the other in that group. The difference in the talocrural angle between the injured and normal sides was the only statistically significant radiographic indicator of a good prognosis.", "Intertrochanteric fractures are composed of different anatomic patterns that vary in their degree of stability following open reduction and internal fixation. A particularly unstable group is classified as AO/OTA 31-A3, with the fracture pattern described as reverse oblique or transverse. The purpose of this study was to compare the results of intramedullary fixation with those of plate fixation for these intertrochanteric fractures in elderly patients.\n Thirty-nine elderly patients with AO/OTA 31-A3 intertrochanteric fractures of the femur were randomized into two treatment groups and were followed for a minimum of one year. The nineteen patients in Group I were treated with a 95 fixed-angle screw-plate (Dynamic Condylar Screw), and the twenty patients in Group II were treated with an intramedullary nail (Proximal Femoral Nail). The treatment groups were comparable with regard to all demographic and injury variables.\n Patients treated with an intramedullary nail had shorter operative times, fewer blood transfusions, and shorter hospital stays compared with those treated with a 95 screw-plate. Implant failure and/or nonunion was noted in seven of the nineteen patients who had been treated with the 95 screw-plate. Only one of the twenty fractures that had been treated with an intramedullary nail did not heal.\n The results of our study support the use of an intramedullary nail rather than a 95 screw-plate for the fixation of reverse oblique and transverse intertrochanteric fractures in elderly patients." ]

[ "10448830", "8232945", "1907907", "11407953", "8082624", "3514204", "8956924", "17382827", "10958046" ]

[ "Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, placebo-controlled study. Gabapentin Paediatric Study Group.", "Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebo-controlled, parallel-group study. The US Gabapentin Study Group No. 5.", "Double-blind study of Gabapentin in the treatment of partial seizures.", "A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy.", "Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. The International Gabapentin Study Group.", "Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy.", "Vigabatrin vs. carbamazepine monotherapy in newly diagnosed focal epilepsy: a randomized response conditional cross-over study.", "The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.", "Gabapentin in the prophylaxis of migraine: a double-blind randomized placebo-controlled study." ]

[ "To evaluate the efficacy and safety of gabapentin (Neurontin; GBP) as add-on therapy for refractory partial seizures in paediatric patients aged 3-12 years.\n After a 6-week baseline period, 247 patients (54 centres) entered a 12-week double-blind phase and were randomized to receive either GBP (t.i.d., titrated to 23-35 mg/kg/ day) or placebo. Seizure activity and type were recorded daily. Efficacy variables included Response Ratio (RRatio), responder rate, and percentage change in frequency (PCH) for all partial seizures; PCH and RRatio for individual types of partial seizures; and investigator and parent/guardian global assessments of seizure frequency and patient well-being.\n RRatio for all partial seizures was significantly lower (better) for GBP-treated patients (p = 0.0407). Responder rate favored GBP, but the difference between treatment groups was not statistically significant. Median PCH for all partial seizures for the GBP treatment group (-17.0%) was better than that for the placebo group (-6.5%). Median PCH for specific seizure types showed GBP to be most effective in controlling complex partial seizures (-35%) and secondarily generalized seizures (-28%) when compared with placebo (-12%, +13%, respectively). A greater percentage of GBP-treated patients exhibited improvement according to investigator and parent/guardian global assessments, with a statistically significant difference observed in the parent/guardian global assessment of seizure-frequency reduction (p = 0.046). Three GBP patients and one placebo patient were seizure free during the double-blind treatment period. GBP was well tolerated.\n GBP was effective and well tolerated as an add-on therapy for partial seizures in paediatric patients with previously drug-resistant seizures.", "Gabapentin, administered as add-on therapy, was safe and effective in this 12-week, multicenter, placebo-controlled, parallel-group study in 306 patients with refractory partial epilepsy. For patients in each gabapentin treatment group (600, 1,200, or 1,800 mg/d), the mean response ratio was significantly better than that of a placebo group. The percentage of patients achieving at least a 50% reduction in seizure frequency was 8% among placebo-treated patients and ranged from 18% to 26% for patients who received gabapentin. Adverse events were generally mild and transient and occurred at a slightly higher frequency among patients receiving gabapentin than among those receiving placebo. Gabapentin did not affect the serum concentrations of concurrent antiepileptic drugs and was not regularly associated with any deviations in clinical laboratory values. Gabapentin's low inherent toxicity and its lack of drug interactions make it an ideal candidate for use as add-on therapy in patients with refractory partial epilepsy.", "Forty-three patients completed a double-blind, placebo-controlled study of Gabapentin (GBP) as add-on therapy in partial and secondarily generalized seizures. All patients were followed for an initial 3-month baseline period, after which they were randomly allocated to receive either a placebo or 900 or 1,200 mg/day GBP for 3 months. A statistically significant difference in seizure frequency from the baseline to the treatment phase was noted between patients receiving placebo and GBP 1,200 mg, in whom seizure frequency decreased 57%. The GBP dosage of 900 mg appeared to be ineffective. A close relationship was observed between the serum GBP concentrations and the GBP dosage based on the seizure frequency. Serum GBP concentrations greater than 2 micrograms/ml resulted in a lower frequency of seizures. The adverse effects were minor and consisted mainly of transient drowsiness. GBP appears to be effective in the treatment of partial epileptic seizures in a dosage-related manner.", "The aim of this study was to evaluate the efficacy and safety of gabapentin in patients with learning disabilities and resistant epilepsy, comparing the effects of gabapentin with lamotrigine on efficacy, behaviour and mood. An open-label, randomized, parallel group, multicentre add-on study comparing gabapentin with lamotrigine in 109 patients with drug-resistant localization-related epilepsy and learning disabilities was conducted: 39 patients were randomized to gabapentin and 44 to lamotrigine. The study population had a range of learning disabilities and severe partial epilepsy. The percentage of patients achieving a greater than or equal to 50% reduction in seizure frequency on gabapentin was 50%, (mean reduction in seizures was 51%). Compared to 48.6% of lamotrigine patients, no statistically significant treatment differences could be identified. The safety profile of both drugs was consistent with that seen in previous clinical trials. Carer-rated visual analogue scales detected significant improvements (P< 0.05) for the gabapentin-treated patients in seizure severity, attention, general health and sleeping pattern, while for lamotrigine seizure severity improved significantly. For learning disabled patients with resistant epilepsy, gabapentin and lamotrigine provide safe and effective treatment, with positive benefits on behaviour.", "A multicenter, double-blind, randomized, placebo-controlled study evaluated the efficacy and safety of gabapentin (Neurontin, GBP) as add-on therapy in 272 patients with refractory partial seizures who were receiving one to two standard antiepileptic drugs (AEDs). Efficacy assessments compared the frequency of partial seizures during the 12-week treatment phase (T) and the 12-week baseline period (B). The primary analysis compared data for patients receiving GBP 900 mg/day with placebo; the GBP 1,200-mg/day group provided dose-response data. Efficacy criteria were percentage of change in seizure frequency (PCH), responder rate (percentage of patients with > or = 50% reduction in seizure frequency), and response ratio, where RRatio = (T-B)/(T + B). Median PCH was -21.8% in the 900-mg/day group and -17.8% in the 1,200-mg/day group as compared with -0.3% in the placebo group. Responder rate was 22.9% in the 900-mg/day group and 10.1% in the placebo group (p = 0.020, Fisher's exact test). Adjusted mean RRatio was -0.136 in the 900-mg/day group and -0.025 in the placebo group (p = 0.0046, analysis of variance ANOVA). Results showed slightly greater improvement for the 1,200-mg/day than for the 900-mg/day group (RRatio = -0.157, responder rate 28.0%). Adverse events (AE) occurred in 69% of patients in the 900-mg/day group and in 64% in the 1,200-mg/day group as compared with 52% in patients receiving placebo as add-on therapy. The most frequent AE among patients treated with GBP were somnolence, dizziness, and fatigue. Clinical laboratory evaluations showed no clinically important trends and no evidence of hepatic or hematopoietic effects.(ABSTRACT TRUNCATED AT 250 WORDS)", "Vigabatrin (GVG) (3 g/day) and placebo were compared as an add-on to standard therapy in therapy-resistant epileptic patients using a double-blind crossover design with randomized treatment allocation. Twenty-three patients entered the trial, with four dropping out due to either increased seizure frequency following the cross-over from GVG to placebo (n = 1), intolerance to GVG therapy (n = 2), or poor seizure record (n = 1). Of the 19 patients who completed the study, 17 had partial seizures, eight of whom had secondary generalization and two who had primary generalized seizures. Compared with placebo, GVG was associated with a significant reduction in seizure frequency (p less than 0.01), with 11 of 19 patients experiencing greater than 50% reduction in weekly seizure occurrence, two showing a 25-50% reduction, four unchanged, and two showing an increase in seizures. Global efficacy ratings were greater in the GVG period for 15 patients (p less than 0.05) compared with one in whom there was no period difference and two in whom ratings were higher in the placebo period. Fourteen of the 19 patients indicated a preference for the GVG period. Adverse effects observed during GVG treatment were generally mild and consisted of drowsiness, confusion, nausea, irritability, and constipation. No clinically significant alterations in laboratory test results were observed. No treatment-related changes in plasma concentrations of concomitant antiepileptic drugs were noted. These results confirm the antiepileptic efficacy of oral GVG in refractory epileptics.", "The clinical efficacy and safety of vigabatrin (VGB) as add-on therapy for pharmaco-resistant focal epilepsies is well established. However, for an objective evaluation, the effects of the drug in the monotherapy of newly diagnosed subjects should be determined. With this aim, VGB was compared, in a randomized, response conditional cross-over study, with carbamazepine (CBZ), the most widely prescribed drug in focal epilepsies. Fifty-one patients with complex partial (CP) seizures were randomly assigned to either the VGB or the CBZ group and evaluated after an initial 4 month period. The cross-over to the alternative drug was carried out, for an analogous period, only in cases with persisting seizures or in the presence of intolerable side effects. Patients who did not respond to either drug were subsequently treated with a combination of VGB and CBZ. No significant difference was revealed in the efficacies of VGB and CBZ; a complete control of seizures was obtained in 17/37 patients (45.9%) treated with VGB and in 20/39 patients (51.3%) treated with CBZ. The side effects were somewhat more frequent (41%) and severe with CBZ than with VGB (21.6%). The power to detect a 20% difference between the two drugs was 75%. The combination of the two drugs suppressed the seizures in 5 out of 14 resistant cases. The preliminary results in this small number of patients are encouraging and suggest that VGB may be considered as a first-line drug for epilepsy with CP seizures and as a valid alternative when other monotherapies are ineffective or poorly tolerated.", "Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes.\n SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748.\n For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine.\n Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.", "Gabapentin is an antiepileptic drug of new generation that increases brain GABA levels. We report the results of a three-month randomised double-blind placebo-controlled study on the effects of gabapentin in the prophylaxis of patients with migraine meeting the IHS criteria.\n We treated 63 patients suffering from migraine with or without aura. Patients treated their attack at home using symptomatic drugs and clinical assessment was recorded on a diary. After a washout of 8 week from any other prophylactic treatment, all patients were treated with 1200 mg/day of gabapentin; this is our therapeutic plan: 400 mg/day from 1st to 3rd day, 800 mg/day from 4th to 6th day and 1200 mg/day from 7th day.\n No patients withdrew, gabapentin was well tolerated; adverse events (somnolence, dizziness, tremor, fatigue and ataxia) generally were transient and mild to moderate in severity and in 13 patients (27%) only occurred. At the end of treatment, in such case, we reported a significative reduction of frequency and intensity of migraine in 30 patients treated with gabapentin.\n Our observations indicate that gabapentin is well tolerated by patients and that reduces headache frequency and use of symptomatic drugs in both groups. Gabapentin shows to have an effective therapeutic action in the prophylactic treatment of migraine." ]

[ "2512486", "9113009", "12081581", "8092094", "1984187", "2767740", "3703632", "11953922", "11730397" ]

[ "The effect of protein restriction on the progression of renal insufficiency.", "Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood.", "Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy.", "Effect of moderate dietary protein restriction on the progression of overt diabetic nephropathy: a 6-mo prospective study.", "Effect of restricting dietary protein on the progression of renal failure in patients with insulin-dependent diabetes mellitus.", "Effect of mid-day meal programme on physical growth & mental function.", "Supplementation with human milk protein improves growth of small premature infants fed human milk.", "Severe dietary protein restriction in overt diabetic nephropathy: benefits or risks?", "Resistance training to counteract the catabolism of a low-protein diet in patients with chronic renal insufficiency. A randomized, controlled trial." ]

[ "Dietary protein intake may be an important determinant of the rate of decline in renal function in patients with chronic renal insufficiency. We conducted a prospective, randomized study of the efficacy of protein restriction in slowing the rate of progression of renal impairment. The study lasted 18 months and included 64 patients with serum creatinine concentrations ranging from 350 to 1000 micromol per liter. The patients were randomly assigned to follow either a regular diet or an isocaloric protein-restricted diet (0.4 g of protein per kilogram of the body weight per day). Blood-pressure levels and the balance between calcium and phosphate were similar in the two groups. End-stage renal failure developed in 9 of the 33 patients (27 percent) who followed the regular diet during the study, as compared with 2 of the 31 patients (6 percent) who followed the protein-restricted diet (P less than 0.05). The mean (+/- SE) glomerular filtration rate, as measured by the clearance of 51Cr bound to EDTA, fell from 0.25 +/- 0.03 to 0.10 +/- 0.05 ml per second (P less than 0.01) in the group on the regular diet, whereas it fell from 0.23 +/- 0.04 to 0.20 +/- 0.05 ml per second (P not significant) in the group on the protein-restricted diet. We conclude that dietary protein restriction is effective in slowing the rate of progression of chronic renal failure.", "Some studies have suggested that a low-protein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF.\n A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2-18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation--i.e., 0.8-1.1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study.\n The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group -9.7 [SD 8.0] vs -10.7 [11.8] mL/min per 1.73 m2; non-progressive group -2.5 [7.5] vs -4.3 [10.0] mL/min per 1.73 m2). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R2 = 0.259) and systolic blood pressure (partial R2 = 0.087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year.\n A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR.", "Recent data suggest that dietary protein restriction improves survival and delays the progression to end-stage renal disease (ESRD) in non-diabetic nephropathies. The purpose of our study was to determine the effect of dietary protein restriction on survival and progression to ESRD in diabetic nephropathy.\n A four-year prospective, controlled trial with concealed randomization was performed comparing the effects of a low-protein diet (0.6 g/kg/day) with a usual-protein diet. The study included 82 type 1 diabetic patients with progressive diabetic nephropathy [pre-study mean decline in glomerular filtration rate (GFR) 7.1 mL/min/year (95% CI, 5.8 to 8.5)]. The main outcome measures were decline in GFR and development of ESRD or death.\n During the follow-up period the usual-protein diet group consumed 1.02 g/kg/day (95% CI; 0.95 to 1.10) as compared with 0.89 (0.83 to 0.95) in the low-protein diet group (P = 0.005). The mean declines in GFR were 3.9 mL/min/year (2.7 to 5.2) in the usual-protein diet group and 3.8 (2.8 to 4.8) in the low-protein diet group. ESRD or death occurred in 27% of patients on a usual-protein diet as compared with 10% on a low-protein diet (log-rank test; P = 0.042). The relative risk of ESRD or death was 0.23 (0.07 to 0.72) for patients assigned to a low-protein diet, after an adjustment at baseline for the presence of cardiovascular disease (P = 0.01). Blood pressure and glycemic control were comparable in the two diet groups during the follow-up period.\n Moderate dietary protein restriction improves prognosis in type 1 diabetic patients with progressive diabetic nephropathy in addition to the beneficial effect of antihypertensive treatment.", "To assess whether moderate dietary protein restriction can delay the progression of overt diabetic nephropathy, 22 subjects with insulin-dependent diabetes mellitus were randomly assigned to an unrestricted protein diet (> 1.6 g.kg body wt-1.d-1) or a moderately protein-restricted diet (0.8 g.kg body wt-1.d-1) and followed prospectively for six mo. Direct isotope methods were used to assess renal function. Protein intake was assessed by measurement of urinary urea nitrogen. The two groups were well-matched for age, sex, duration of diabetes, glycemic control, blood pressure, and degree of renal insufficiency. Patients consuming the unrestricted protein diet (n = 11) showed a progressive decline in glomerular filtration rate of 1.3 mL.min-1.mo-1 with no change in proteinuria. Patients consuming the moderately protein-restricted diet showed a marked decrease in the degree of proteinuria (2.15-1.13 g/d, P = 0.036) and a stabilization of glomerular filtration rate. This occurred independently of changes in blood pressure or glycemic control. Moderate dietary protein restriction can ameliorate progression of overt diabetic nephropathy.", "Restriction of dietary protein may slow the progression of renal failure in diverse renal diseases, but the extent to which such a diet is beneficial in patients with diabetic nephropathy is uncertain.\n We studied the effect of reduced intake of protein and phosphorus on the progression of renal disease in 35 patients with insulin-dependent (Type I) diabetes mellitus and clinically evident nephropathy. The low-protein, low-phosphorus diet contained 0.6 g of protein per kilogram of ideal body weight per day, 500 to 1000 mg of phosphorus, and 2000 mg of sodium. The control diet consisted of the patient's prestudy diet with the stipulation that it contain 2000 mg of sodium and at least 1 g of protein per kilogram per day and 1000 mg of phosphorus. Renal function was assessed by measurement of iothalamate and creatinine clearances at intervals of 3 to 6 months, and the patients were followed for a minimum of 12 months (mean, 34.7). The declines in mean glomerular filtration rates were compared between groups by linear-regression analysis of the glomerular filtration rate as a function of time.\n The patients who followed the study diet for a mean of 37.1 months had declines in iothalamate clearance of 0.0043 ml per second per month and in creatinine clearance of 0.0055 ml per second per month. The comparable values in the control group were 0.0168 and 0.0135, respectively (P less than 0.05). Blood pressure was well controlled, and the degree of glycemic control was comparable in both groups.\n Dietary restriction of protein and phosphorus can retard the progression of renal failure in patients with Type I diabetes mellitus who have nephropathy. We believe that wider use of this treatment is indicated.", "The effect of food supplementation in rural primary school children was studied on physical growth and mental functions. Children (146) received 450-500 calories with 10-12 g of protein for an average of 172 days a year, for 2 yr (1984-1986). Height was found not to differ significantly in the supplemented group as compared to controls. However, there was marginally better weight gain. More children in the supplemented group remained in grade I in contrast to the controls who shifted to grade II nutritional status after 2 yr. Children receiving the supplementation showed marginal increment in full scale, verbal and performance IQ. The improvement was significant for all subtests except for comprehension and maze tests. The observations on unstructured Piagetian developmental tasks also indicated that the performance of children on task conservation of liquid was improved marginally after supplementation. However, on Bender Gestalt test, no change was observed. The scores on arithmetic achievement test showed improvement of 12-14 points in the supplementation group. It appears that nutrition supplementation is beneficial for better school attendance, and reduction in the drop out rate; it also improves intelligence and cognitive function to a marginal extent. However, as this age group falls in the slow growth period, no catch up was observed in physical growth.", "We investigated the influence of human milk protein and medium-chain triglyceride supplementations of human milk feedings on the growth of very low birth weight infants during their first weeks of life. A group of 44 preterm infants with birth weights of less than 1,520 g and a mean gestational age of 30.3 weeks was randomly divided into four groups to receive plain human milk or human milk supplemented with human milk protein (0.9 g/dL), with medium-chain triglycerides (1 g/dL), or with both. The medium-chain triglyceride oil supplementation did not influence the growth of these infants. The infants given supplementary protein gained weight faster during weeks 4 to 6 than those without (18.5 +/- 0.7 v 15.1 +/- 0.6 g/kg/d; mean +/- SEM; P = .001). After 4 weeks of age the infants given supplementary protein had a mean weight gain equal to the mean intrauterine rate, in contrast to the infants of the other groups, who grew more slowly until age 6 weeks. Furthermore, we found a correlation between serum albumin concentration and weight gain during the seventh week of life (P = .018). The length growth velocity for the infants with protein supplementation was 0.99 +/- 0.06 cm/wk (mean +/- SEM) and for those without 0.83 +/- 0.05 cm/wk (P = .043). There was no difference in growth of head circumference between the groups. We conclude that human milk protein supplementation improves the growth of small premature infants fed human milk, and that the protein concentration of bank milk is insufficient for their adequate growth.", "To evaluate whether restricting protein intake may delay the progression of chronic renal failure caused by overt diabetic nephropathy and also whether this increases the risk of malnutrition.\n Prospective clinical trial.\n Nephrology outpatients.\n Sixty-nine patients (32 affected by type 1 and 37 by type 2 diabetes, all treated with insulin) affected by both overt diabetic nephropathy and hypertension.\n The study was started once hypertension and glycemia had been under control for at least 3 months. Two groups of patients, matched for similar mean glomerular filtration rate value and nutritional status, were studied: a low-protein diet (0.6 g/kg/d) was randomly prescribed to 35 patients, whereas in the other 34 patients a free diet intake was maintained for 12 months.\n Renal function and nutritional status.\n The protein intake was significantly different in the 2 groups of patients, whereas the average decline of glomerular filtration rate during the follow-up was comparable. In the low-protein diet group, serum prealbumin concentration significantly decreased after 9 months, whereas serum albumin decreased at the end of the study.\n Severe dietary protein restriction does not seem to delay the progression of renal disease in patients with overt diabetic nephropathy, whereas it may induce malnutrition.\n Copyright 2002 by the National Kidney Foundation, Inc.", "Chronic renal insufficiency leads to muscle wasting, which may be exacerbated by low-protein diets prescribed to delay disease progression. Resistance training increases protein utilization and muscle mass.\n To determine the efficacy of resistance training in improving protein utilization and muscle mass in patients with chronic renal insufficiency treated with a low-protein diet.\n Randomized, controlled trial.\n Tufts University, Boston, Massachusetts.\n 26 older patients with moderate renal insufficiency (17 men, 9 women) who had achieved stabilization on a low-protein diet.\n During a run-in period of 2 to 8 weeks, patients were instructed and their adherence to the low-protein diet (0.6 g/kg of body weight per day) was evaluated. They were randomly assigned to a low-protein diet plus resistance training (n = 14) or a low-protein diet alone (n = 12) for 12 weeks.\n Total body potassium, mid-thigh muscle area, type I and II muscle-fiber cross-sectional area, and protein turnover.\n Mean protein intake was 0.64 +/- 0.07 g/kg per day after stabilization. Total body potassium and type I and II muscle-fiber cross-sectional areas increased in patients who performed resistance training by a mean (+/-SD) of 4% +/- 8%, 24% +/- 31%, and 22% +/- 29%, respectively, compared with those who did not. Leucine oxidation and serum prealbumin levels also improved significantly. Patients assigned to resistance training maintained body weight compared with those who were not. Improvement in muscle strength was significantly greater with resistance training (32% +/- 14%) than without (-13% +/- 20%) (P < 0.001).\n By improving muscle mass, nutritional status, and function, resistance training seems to be effective against the catabolism of a low-protein diet and uremia in patients with renal failure." ]

[ "10575581", "16055454", "10966992", "11228214", "12930586", "12042269", "12093851", "11779600", "14507836" ]

[ "Clinical outcome of day 2 versus day 3 embryo transfer using serum-free culture media: a prospective randomized study.", "Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study.", "Day 5 versus day 3 embryo transfer: a controlled randomized trial.", "A prospective, randomized study comparing day 2 and day 3 embryo transfer in human IVF.", "Day 3 versus day 5 embryo transfer: a prospective randomized study.", "A prospective randomized study: day 2 versus day 5 embryo transfer.", "Day 3 embryo transfer with combined evaluation at the pronuclear and cleavage stages compares favourably with day 5 blastocyst transfer.", "Blastocyst culture and transfer: a step toward improved in vitro fertilization outcome.", "Similar delivery rates in a selected group of patients, for day 2 and day 5 embryos both cultured in sequential medium: a randomized study." ]

[ "The objective was to evaluate whether extending the embryo culture period from 2 to 3 days would yield a more optimal selection of viable embryos, thereby increasing the implantation and live birth rates.\n Patients undergoing in vitro fertilization with at least one oocyte fertilized were prospectively randomized to 2 or 3 days of embryo culture in serum-free media. On the basis of their morphology and cleavage rate, a maximum of three embryos was selected for transfer.\n Embryos transferred on day 2 or day 3 were similar morphologically, however, a higher proportion of retarded embryos was observed on day 3. The implantation rate was 15.8 and 14.3% for day 2 and day 3 transfers, respectively. The increase in live birth rate from 18.5 to 22.6%, possibly suggesting a better embryo selection on day 3, was not statistically significant.\n Extending the embryo culture period from 2 to 3 days had no effect on implantation and live birth rates.", "In a randomized controlled trial, we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good-quality embryos on day 3.\n Multifollicular ovarian stimulation was performed with a GnRH agonist in 44% of patients and with a GnRH antagonist in 56%. Overall, 164 patients younger than 37 years fulfilled embryo quality criteria (at least four having at least six cells on the morning of day 3, maximum 20% anucleate fragments) on the third day of culture and were randomized to the day 3 (n = 84) or day 5 (n = 80) groups. Equal numbers of embryos (n = 2) were transferred in each group.\n Demographics, stimulation parameters and embryological data were comparable in the two groups. Blastocyst-stage transfer resulted in a significantly higher ongoing pregnancy rate [51.3 versus 27.4%; odds ratio (OR) 2.78, 95% confidence interval (CI) 1.45-5.34] and live birth rate (47.5 versus 27.4%; OR 2.40, 95% CI 1.25-4.59) compared with day-3 embryo transfer. A high twin birth rate was observed in both groups (36.8 versus 30.4%; P > 0.05).\n A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer.", "Blastocyst transfer has been suggested to improve implantation rate without affecting pregnancy rate. The aim of this study was to compare the pregnancy and implantation rates of day 3 and 5 transfers in a prospective randomized manner. Patients with four or more zygotes were randomly allocated on day 1 to either day 3 or 5 transfers. Fertilization was achieved through regular IVF or intracytoplasmic sperm injection. Zygotes were kept in Medicult IVF medium for day 3 transfers and transferred into G1.2 and G2.2 on day 1 and 3 respectively for day 5 transfers. The morphologically best two or three embryos or blastocysts were chosen for transfer in both groups. Overall pregnancy rates per embryo transfer were the same (39%) in day 3 and 5 transfers. Implantation rates were 21 and 24% for day 3 and 5 transfers respectively. The pregnancy and implantation rates for day 5 transfers were significantly affected by the availability of at least one blastocyst to transfer and the number of zygotes. The number of good quality embryos on day 3 also significantly affected pregnancy and implantation rates on day 5 transfers. Multiple gestation rate, number of abortions and ongoing pregnancies were similar in both groups. In conclusion, day 3 and 5 transfer had similar pregnancy, implantation and twinning rates. Currently, day 5 transfers have no advantages over day 3 transfers.", "It is believed that delayed transfer of embryos after IVF allows for a better selection of good quality embryos. Hence, the number of embryos and all other prognostic factors being equal, transfer of day 3 embryos should be associated with higher implantation and pregnancy rates than transfer of day 2 embryos. To investigate this hypothesis, a prospective randomized study was carried out to compare implantation and pregnancy rates between day 2 and day 3 transfers. The relationship between the embryo quality score of day 2 and day 3 embryos and their respective implantation rates was also analysed. In a 2 year period all patients undergoing infertility treatment and in whom at least seven normally fertilized oocytes were obtained were included in the study. A minimization procedure was performed taking into account the patient's age and the method of fertilization (IVF or intracytoplasmic sperm injection). By using a uniform policy of embryo transfer, the number of embryos transferred was similar in both groups. The outcome parameters were embryo quality, implantation and pregnancy rates. No difference was observed in implantation and pregnancy rates between transfers on day 2 versus day 3 (23.8 versus 23.8% and 47.9 versus 46.8% respectively). The incidence of embryos of moderate to poor quality was higher in embryos cultured for 3 days compared with those cultured for 2 days. It is concluded that the outcomes of embryo transfer in terms of implantation and pregnancy rates are comparable for day 2 and day 3 embryos, although the overall embryo quality score decreases when embryos are kept in culture till day 3.", "Transfer of embryos at the blastocyst stage has been associated with exceptionally high implantation rates. There are, however, only a few prospective randomized studies comparing day 3 versus day 5 embryo transfer. Furthermore, the number of embryos replaced in the day 3 group transfer is often higher than the number of blastocysts replaced, thereby affecting implantation rates. A total of 118 patients undergoing standard IVF/intracytoplasmic sperm injection who had developed at least three 8-cell embryos showing <20% extracellular fragmentation on day 3 were randomized for day 3 or day 5 transfer. A maximum of two embryos were replaced. In this prospective, randomized study the implantation and pregnancy potential of embryos transferred on day 3 or day 5 were compared. Equal numbers of embryos were replaced in the two groups. There was no statistically significant difference between day 3 and day 5 transfer regarding positive human chorionic gonadotrophin rates (70 versus 67%), clinical pregnancy rates (61 versus 51%), implantation rates (44 versus 37%), twinning rates (42 versus 41%) and rates of early pregnancy loss (15 versus 29%). Transfer of embryos on day 3 or 5 showed similar implantation rates when equal numbers of embryos were transferred. Embryo transfer at the blastocyst stage seems to have no advantage over day 3 transfer in patients with more than two 8-cell embryos showing less than 20% fragmentation on day 3.", "This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers.\n Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred.\n The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%).\n This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers.", "The respective advantages of day 3 and day 5 embryo transfer are a matter of debate. Previous comparisons did not include pronuclear stage zygote scoring and cumulative success rates (fresh and cryopreserved embryos).\n Patients were randomized prospectively for day 3 or day 5 embryo transfer. Day 3 embryos were selected for transfer and cryopreservation by using combined evaluation at the pronuclear and cleavage stages.\n There was no difference between day 3 and day 5 fresh embryo transfers as to the rates of pregnancy (58 versus 62%), clinical pregnancy (56 versus 58%), delivery (50 versus 48%), implantation (35 versus 38%) and birth (33 versus 36%) rates. The corresponding values for cryopreserved embryo transfers were also similar. However, day 3 embryo transfer compared favourably with day 5 transfer when the pregnancy (90 versus 66%), clinical pregnancy (85 versus 62%) and delivery (77 versus 52%) rates were calculated per oocyte recovery attempt.\n With a selected population of good prognosis patients and our embryo selection criteria, the implantation potential of day 3 and day 5 embryos is equal. Per oocyte recovery attempt, day 3 transfer is more clinically efficient than day 5 transfer, but at least one transfer of cryopreserved embryos is necessary to manifest this superiority.", "To evaluate the efficacy of blastocyst culture and transfer in human in vitro fertilization (IVF) as compared to day 3 embryo transfer.\n Prospective randomized trial.\n Private assisted reproduction unit.\n A total of 162 IVF patients were included in the day 3 embryo transfer (n = 82) and blastocyst transfer (n = 80) groups.\n Embryo transfer on day 3 after culture in the standard culture media and blastocyst transfer on day 5 or 6 after culture in the sequential culture media.\n Implantation and pregnancy rates, multiple gestation rate.\n The implantation rate for embryos transferred at the blastocyst stage was significantly higher than that for embryos transferred on day 3 (26% vs. 13%). The viable pregnancy rate was similar in both groups (29% vs. 26%). Significantly fewer embryos were required for transfer at the blastocyst stage compared with day 3 embryo transfer (2.0 +/- 0.1 vs. 3.5 +/- 0.63). The high-order multiple gestation rate was significantly less with the blastocyst transfer than with the day 3 embryo transfer (4% vs. 19%).\n With the use of blastocyst culture, a few embryos can be transferred without decreasing the overall pregnancy rate. This may reduce multiple gestations and improve human IVF outcome.", "The existence of a real benefit of blastocyst transfer is still a matter of debate. The aim of this study was to compare, in a prospective randomized trial, the outcome of day 2 and day 5 transfer of human embryos cultured in an 'in-house' sequential medium.\n A total of 193 cycles from 171 patients with less than four previous IVF cycles, <39 years old and with four or more zygotes on day 1, were randomly allocated to day 2 (94 cycles) or day 5 (99 cycles) transfer. Zygotes were kept in fertilization medium until 18 h post-fertilization and then placed in a 'glucose-free' cleavage medium. Embryos allocated for day 5 transfer were placed in a blastocyst medium 66 h post-fertilization. Two or three embryos were replaced according to the morphology.\n A mean (+/- SEM) number of 2.1 +/- 0.4 and 1.9 +/- 0.3 embryos were replaced on day 2 and day 5 (P < 0.001) respectively. Delivery rates per transfer were 44.1 and 37.1% [P = not significant (NS)], implantation rates were 31.4 and 29.4% (NS) and multiple delivery rates 22 and 36% (NS) for day 2 and day 5 groups respectively. Ten patients (10.1%) had no blastocysts available for transfer.\n No clear benefits were observed using blastocyst transfer for patients aged <39 years who had had less than four previous IVF cycle attempts." ]

[ "11226090", "11818760", "18679598", "10081532", "16428565", "2181138", "12855628", "18043058", "12705488" ]

[ "The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery.", "Electroacupuncture prophylaxis of postoperative nausea and vomiting following pediatric tonsillectomy with or without adenoidectomy.", "Evaluation of transcutaneous electroacupoint stimulation with the train-of-four mode for preventing nausea and vomiting after laparoscopic cholecystectomy.", "Effect and placebo effect of acupressure (P6) on nausea and vomiting after outpatient gynaecological surgery.", "Transcutaneous acupoint electrical stimulation with the ReliefBand for the prevention of nausea and vomiting during and after cesarean delivery under spinal anesthesia.", "Postoperative nausea is relieved by acupressure.", "Effect of acupuncture compared with placebo-acupuncture at P6 as additional antiemetic prophylaxis in high-dose chemotherapy and autologous peripheral blood stem cell transplantation: a randomized controlled single-blind trial.", "Monitoring of neuromuscular blockade at the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting.", "Effect of acupressure on postoperative nausea and vomiting in laparoscopic cholecystectomy." ]

[ "Nonpharmacologic techniques may be effective in preventing postoperative nausea and vomiting (PONV). This sham-controlled, double-blinded study was designed to examine the antiemetic efficacy of transcutaneous acupoint electrical stimulation (TAES) in a surgical population at high risk of developing PONV. We studied 221 outpatients undergoing laparoscopic cholecystectomy with a standardized general anesthetic technique in this randomized, multicenter trial. In the TAES group, an active ReliefBand(Woodside Biomedical, Inc., Carlsbad, CA) device was placed at the P6 acupoint, whereas in the Sham and Placebo groups, an inactive device was applied at the P6 acupoint and at the dorsal aspect of the wrist, respectively. The ReliefBand was applied after completion of electrocautery and remained in place for 9 h after surgery. The incidence of PONV and need for \"rescue\" medication were evaluated at predetermined time intervals. TAES was associated with a significantly decreased incidence of moderate-to-severe nausea as denoted on the Functional Living Index-Emesis score for up to 9 h after surgery (5%-11% for the TAES group vs 16%-38% [P < 0.05] and 15%-26% [P < 0.05] for Sham and Placebo groups, respectively). TAES was also associated with a larger proportion of patients free from moderate to severe nausea symptoms (73% vs 41% and 49% for Sham and Placebo groups, respectively; P < 0.05). However, there were no statistically significant differences among the three groups with regard to incidence of vomiting or the need for rescue antiemetic drugs. We conclude that TAES with the ReliefBand at the P6 acupoint reduces nausea, but not vomiting, after laparoscopic cholecystectomy.\n Transcutaneous acupoint electrical stimulation at the P6 acupoint reduced postoperative nausea, but not vomiting, in outpatients undergoing laparoscopic cholecystectomy procedures.", "Electrical stimulation of acupuncture point P6 reduces the incidence of postoperative nausea or vomiting (PONV) in adult patients. However, acupressure, laser stimulation of P6, and acupuncture during anesthesia have not been effective for reducing PONV in the pediatric population. The authors studied the effect of electrical P6 acupuncture in awake pediatric patients who had undergone surgery associated with a high incidence of PONV.\n Patients aged 4-18 yr undergoing tonsillectomy with or without adenoidectomy were randomly assigned to acupuncture, sham acupuncture, or control groups. Acupuncture needles at P6 and a neutral point were placed while patients were anesthetized, and low-frequency electrical stimulation was applied to these points for 20 min in the recovery room while the patients were awake (P6 Acu group). This treatment was compared with sham needles along the arm at acupuncture points not associated with antiemesis (sham group) and a no-needle control group. The arms were wrapped to prevent identification of treatment group, and anesthetic, analgesic, and surgical technique were standardized. Assessed outcomes were occurrence of nausea, occurrence and number of episodes of vomiting, time to vomiting, and use of antiemetic rescue medication.\n One hundred twenty patients were enrolled in the study, 40 per group. There were no differences in age, weight, sex, or opioid administration between groups. The PONV incidence was significantly lower with P6 acupuncture (25 of 40 or 63%; odds ratio, 0.135; number needed to treat, 3.3; P < 0.001) compared with controls (37 of 40 or 93%). Sham puncture had no effect on PONV (35 of 40 or 88%; P = not significant). Occurrence of nausea was significantly less in P6 Acu (24 of 40 or 60%; odds ratio, 0.121; P < 0.01), but not in the sham group (34 of 40 or 85%) compared with the control group (37 of 40 or 93%). Vomiting occurred in 25 of 40 or 63% in P6 Acu; 35 of 40 or 88% in the sham group, and 31 in 40 or 78% in the control group (P = not significant). Patients receiving sham puncture vomited significantly earlier (P < 0.02) and needed more rescue treatment (33 of 40 or 83%; odds ratio, 3.48; P < 0.02) compared with P6 Acu (23 of 40 or 58%) and the control group (24 of 40 or 60%).\n Perioperative P6 electroacupuncture in awake patients significantly reduced the occurrence of nausea compared with the sham and control groups, but it did not significantly reduce the incidence or number of episodes of emesis or the use of rescue antiemetics. Sham acupuncture may exacerbate the severity but not the incidence of emesis. The efficacy of P6 acupuncture for PONV prevention is similar to commonly used pharmacotherapies. Its appropriate role in prevention and treatment of PONV requires further study.", "To evaluate the efficacy of transcutaneous electroacupoint stimulation with a train-of-four (TOF) mode for the prevention of postoperative nausea and vomiting (PONV) in the patients undergoing laparoscopic cholecystectomy.\n Ninety-six ASA Grade I - II patients scheduled for laparoscopic cholecystectomy were randomized into Neiguan (P6) electroacupoint stimulation group (treated group) and a placebo control group (placement of electrodes without electroacupoint stimulation). The anesthetic regimen was standardized by needling at Neiguan on the left side and connecting the TOF peripheral nerve stimulator. The incidence of nausea, vomiting, severity, antiemetic dosage and the degree of pain were assessed at 0, 60, 120 min, and 24 h after surgery.\n The incidence of nausea and vomiting, the dose of antiemetics and the occurrence of severe nausea were all significantly lower in the treated group compared with the control group and the score for pain was obviously reduced in patients of the treated group at 24 h post-operation (P<0.05 or P<0.01).\n Transcutaneous electroacupoint stimulation at P6 with the TOF mode could reduce the incidence and severity of nausea and vomiting with analgesic effects.", "Acupuncture and acupressure have previously been reported to possess antiemetic effect. We wanted to investigate the \"true\" and placebo effect of acupressure in prevention of postoperative nausea and vomiting (PONV).\n Sixty women undergoing outpatient minor gynaecological surgery were entered into a double-blind and randomised study. One group received acupressure with bilateral stimulation of P6 (A), a second group received bilateral placebo stimulation (P) and a third group received no acupressure wrist band and served as a reference group (R). PONV was evaluated as number of patients with complete response (no PONV), nausea only or vomiting. In addition, the need for rescue antiemetic medication and nausea after 24 h was registered.\n Complete response was obtained in 11, 11 and 9 patients in groups, A, P and R, respectively. Nine, 7 and 6 patients had nausea before discharge home, and 1, 1 and 8 patients were nauseated (8 vs 1 patient: P < 0.05) 24 h after operation in A, P and R groups, respectively. When compared to placebo acupressure (2 patients vomited and 5 needed rescue), significantly (P < 0.05) fewer needed rescue antiemetic medication after acupressure at P6 (no vomiting or rescue medication). When compared to the observation group (5 vomited and 4 needed rescue antiemetics), significantly fewer vomited after acupressure (P < 0.05)\n In patients undergoing brief gynaecological surgery, placebo effect of acupressure decreased nausea after 24 h but vomiting and need of rescue antiemetics was reduced only by acupressure with the correct P6 point stimulation.", "We randomized 94 patients undergoing cesarean delivery with spinal anesthesia to receive transcutaneous acupoint electrical stimulation using the ReliefBand at the P6 point (active group) or an active ReliefBand applied to the dorsum of the wrist (sham control group). The ReliefBand was applied 30-60 min preoperatively and left in place for 24 h. There was no statistically significant difference between the active and sham control groups in the incidence of intraoperative/postoperative nausea (30% versus 43%/23% versus 41%), vomiting (13% versus 9%/26 versus 37%), need for rescue antiemetics (23% versus 18%/34% versus 39%), or complete response (55% versus 57%/51% versus 34%). There was also no difference between the two groups in nausea scores, number of vomiting episodes, or patient satisfaction with postoperative nausea and vomiting management.", "One hundred and sixty-two general surgical patients were prospectively randomized to one of three treatments for postoperative nausea and vomiting: (1) acupressure using elasticated bands containing a plastic button to apply sustained pressure at the P6 (Neiguan) point above the wrist, (2) control dummy bands without the pressure button and (3) antiemetic injections of prochlorperazine with each opiate given and as required. All patients received papaveretum injections as required for pain, and additional prochlorperazine injections were prescribed if nausea was not controlled in groups 1 and 2. The severity of nausea was assessed using a linear analogue scale and was significantly (P = 0.002) reduced by acupressure on both days 1 and 2, in comparison to both controls and drug treated patients. The incidence of postoperative vomiting, and the need for unplanned antiemetic injections was also reduced by acupressure but this was not statistically significant. Acupressure can work and should be investigated in other clinical situations.", "The purpose is to investigate an additional antiemetic effect to ondansetron with needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture in patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation.\n Eighty patients who were admitted to hospital for high-dose chemotherapy and autologous peripheral blood stem cell transplantation were included into a randomized placebo-controlled single-blind trial. The patients were randomized to receive acupuncture (n = 41) or noninvasive placebo acupuncture (n = 39) at the acupuncture point P6 30 min before first application of high-dose chemotherapy and the day after. All patients received 8 mg ondansetron/day i.v. as basic antiemetic prophylaxis. The main outcome measure was the rate of patients who either had at least one episode of vomiting or required any additional antiemetic drugs on the first 2 days of chemotherapy.\n The main outcome measure showed no significant difference (P = 0.82): 61% failure in the acupuncture group and 64% in the placebo acupuncture group (95% confidence interval of 3% difference: -18.1 and 24.3%). Comparing nausea, episodes of vomiting or retching and number of additionally required antiemetic drugs did not provide any discrepancy with the main result.\n This study suggests that in combination with ondansetron i.v., invasive needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture has no additional effect for the prevention of acute nausea and vomiting in high-dose chemotherapy.", "Electrical stimulation of the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting (PONV). Neuromuscular blockade during general anesthesia can be monitored with electrical peripheral nerve stimulation at the wrist. The authors tested the effect of neuromuscular monitoring over the P6 acupuncture point on the reduction of PONV.\n In this prospective, double-blinded, randomized control trial, the authors investigated, with institutional review board approval and informed consent, 220 women undergoing elective laparoscopic surgery anesthetized with fentanyl, sevoflurane, and rocuronium. During anesthesia, neuromuscular blockade was monitored by a conventional nerve stimulator at a frequency of 1 Hz over the ulnar nerve (n = 110, control group) or over the median nerve (n = 110, P6 group) stimulating at the P6 acupuncture point at the same time. The authors evaluated the incidence of nausea and vomiting during the first 24 h.\n No differences in demographic and morphometric data were found between both groups. The 24-h incidence of PONV was 45% in the P6 acupuncture group versus 61% in the control group (P = 0.022). Nausea decreased from 56% in the control group to 40% in the P6 group (P = 0.022), but emesis decreased only from 28% to 23% (P = 0.439). Nausea decreased substantially during the first 6 h of the observation period (P = 0.009). Fewer subjects in the acupuncture group required ondansetron as rescue therapy (27% vs. 39%; P = 0.086).\n Intraoperative P6 acupuncture point stimulation with a conventional nerve stimulator during surgery significantly reduced the incidence of PONV over 24 h. The efficacy of P6 stimulation is similar to that of commonly used antiemetic drugs in the prevention of PONV.", "To evaluate the effectiveness of acupressure applied at meridian P6 point for prevention of nausea and vomiting in patients undergoing laparoscopic cholecystectomy.\n A randomized double blind study was performed in 50 ASA I and II patients scheduled for laparoscopic cholecystectomy. Patients were divided into two groups; control and placebo. In the control group acupressure was applied at P6 point half an hour before surgery while in the placebo group the acupressure band was tied on meridian P6 point but the plastic bead was placed on the dosum of right forearm away from meridian P6 point. Patients were assessed for nausea and vomiting for six hours after surgery. Anaesthetic technique and postoperative analgesia were standardized for all patients.\n Results showed that the incidence of postoperative nausea and vomiting was 36% in the treatment group and 40% in placebo group, which is statistically insignificant.\n Application of acupressure at P6 point half an hour before induction of anaesthesia does not significantly alter the incidence of postoperative nausea and/or vomiting within 6 hours after surgery." ]

[ "7903180", "16629429", "2390654", "14734433", "17522511", "2258521", "7489218", "9630149", "2651586" ]

[ "Biochemical and physiological parameters of recovery in acute severe head injury: responses to multisensory stimulation.", "The efficacy of multidisciplinary rehabilitation in stable multiple sclerosis patients.", "Coma arousal procedure: a therapeutic intervention in the treatment of head injury.", "Multicentre, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT).", "A prospective randomized controlled trial of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.", "The effect of systematic care planning after acute stroke in general hospital medical wards.", "Design issues of a randomised controlled clinical trial on spinal cord stimulation in critical limb ischaemia. ESES Study Group.", "Traumatic brain injury: efficacy of multidisciplinary rehabilitation.", "The treatment of spontaneous intracerebral hemorrhage. A prospective randomized trial of surgical and conservative treatment." ]

[ "We investigated the efficacy of applying a programme of multisensory stimulation to patients with severe diffuse traumatic brain injury, during their admission to a tertiary neurosurgical intensive care unit. We attempted to determine the nature and extent of any physiological or biochemical changes occurring as a result of the multisensory stimulation in the initial period of their comatose state. The findings were inconclusive with no significant treatment effect demonstrated.", "To evaluate the short-term efficacy of multidisciplinary, inpatient rehabilitation of multiple sclerosis (MS) patients.\n A double-blind, randomized, parallel group design was used. The intervention group were offered comprehensive, multidisciplinary inpatient rehabilitation at the Haslev MS Hospital for an average of 35.5 days, while the control group received no treatment related to the study. All patients were examined in their homes twice with a 10-week interval. The rehabilitation of the intervention group started 2-3 weeks after the first examination and ended 2-3 weeks before the second examination. Impairment was assessed by the Multiple Sclerosis Impairment Scale and the Expanded Disability Status Scale. Disability was assessed by means of Guy's Neurological Disability Scale. Two specific scales were used to assess upper limb function and ambulation: The Nine-Hole Peg Test and timed 10-metre walking. Patients' own perception of bodily pain, bladder symptoms, spasticity, fatigue, impaired walking and transfers were recorded using visual analogue scales. Finally, quality of life was assessed using the Life Appreciation and Satisfaction Questionnaire and the Functional Assessment in Multiple Sclerosis.\n Two hundred and thirty-three patients were screened and of those 38 were included for treatment and 52 as controls.\n We found no statistically significant differences between the two groups in any of the outcome measures.\n Although the study was underpowered, the negative outcome exposes the difficulties in quantitative analyses of the efficacy of multidisciplinary rehabilitation, which is liable to confounding factors such as variation in the indication for treatment, in the placebo effect, and in the reliability and responsiveness of the outcome measures.", "This study reports on the efficacy of a 'coma arousal procedure'. This procedure involved a programme of vigorous sensory stimulation administered to comatose patients by relatives using Comakits. An experimental group of 12 severely head-injured patients received the coma arousal procedure while a matched control group did not. Total duration of coma and weekly Glasgow Coma Scale Scores were recorded for the two groups. Results indicate that the total duration of coma was significantly shorter and that coma lightened more rapidly for the experimental group.", "The provision of nutritional support for patients in intensive care units (ICUs) varies widely both within and between institutions. We tested the hypothesis that evidence-based algorithms to improve nutritional support in the ICU would improve patient outcomes.\n A cluster-randomized controlled trial was performed in the ICUs of 11 community and 3 teaching hospitals between October 1997 and September 1998. Hospital ICUs were stratified by hospital type and randomized to the intervention or control arm. Patients at least 16 years of age with an expected ICU stay of at least 48 hours were enrolled in the study (n = 499). Evidence-based recommendations were introduced in the 7 intervention hospitals by means of in-service education sessions, reminders (local dietitian, posters) and academic detailing that stressed early institution of nutritional support, preferably enteral.\n Two hospitals crossed over and were excluded from the primary analysis. Compared with the patients in the control hospitals (n = 214), the patients in the intervention hospitals (n = 248) received significantly more days of enteral nutrition (6.7 v. 5.4 per 10 patient-days; p = 0.042), had a significantly shorter mean stay in hospital (25 v. 35 days; p = 0.003) and showed a trend toward reduced mortality (27% v. 37%; p = 0.058). The mean stay in the ICU did not differ between the control and intervention groups (10.9 v. 11.8 days; p = 0.7).\n Implementation of evidence-based recommendations improved the provision of nutritional support and was associated with improved clinical outcomes.", "A prospective randomized controlled trial (RCT) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.\n This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT.\n Patients for elective resection for colorectal cancer were offered trial entry. Participants were stratified by sex and requirement for a total mesorectal excision and centrally randomized. Multimodal patients received intravenous fluid restriction, unrestricted oral intake with prokinetic agents, early ambulation, and fixed regimen epidural analgesia. Control patients received intravenous fluids to prevent oliguria, restricted oral intake until return of bowel motility, and weaning regimen epidural analgesia. Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets. Discharge decision was made using pre-agreed criteria. The primary endpoint was postoperative stay, and achievement of independence milestones. Secondary endpoints were postoperative complications, readmission rates, and mortality. Analysis was by intention to treat.\n Seventy patients were recruited. Approximately one fourth underwent TME. Median ages were similar (69.3 vs. 73.0 years). The median stay was significantly reduced in the multimodal group (5 vs. 7 days; P < 0.001, Mann-Whitney U test). Patients in the control arm were 2.5 times as likely to require a postoperative stay of more than 5 days. Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions. There were 2 deaths, both controls.\n This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery. Morbidity and mortality are not increased.", "In a multidisciplinary study comprising 280 patients with acute cerebrovascular disease, the functional capacity was followed from the acute stage onwards with a test battery mainly measuring activities of daily living and motor capacity. Systematized care procedures with written care plans in accordance with the nursing process model, together with a booklet of guidelines in stroke care, were introduced during an experimental period in the care of 173 of the stroke victims. The remaining 107 patients received conventional care. The functional improvements were equal from a statistical standpoint in these two groups. However, in the group, which received special activities, there was a significant decrease in bed days, and a slightly larger number were able to return to their own homes. Compared with another stroke population from the same hospital, measured with the same functional instrument 7 years ago, the patients in this study seemed better off from a functional standpoint. For the individual severely-disabled patient, the care planning procedures seemed to be valuable and an effective way of promoting communication between different units. The difficulties in introducing new routines for documentation are discussed.", "Review of the design of a clinical study to evaluate of the efficacy of epidural spinal cord electrical stimulation (ESES) as compared to best medical treatment in patients with nonreconstructible critical limb ischaemia.\n Randomised controlled clinical trial of pragmatic type, which will be analysed according to the intention-to-treat principle. The treatment strategies are ESES, in addition to best medical treatment, and best medical treatment alone. Patients are followed-up for at least 18 months.\n The ESES-trial is an ongoing multicentre trial in 17 hospitals in The Netherlands.\n Patients with critical limb ischaemia, nonsuitable for either primary intervention or reintervention after failing reconstructions.\n Limb survival, patient survival, quality of life and cost-effectiveness.\n From November 1991 until May 1994 120 patients had been enrolled. Using life-table analysis, at one year 76% of these randomised patients were alive: 41% without amputation and 35% with amputation. Quality of life of the trial patients was low, even compared to other severely ill patient groups, such as liver and heart transplant candidates.\n Considering the high incidence of death and amputation, 18 months of follow-up seems adequate to detect a clinically relevant outcome improvement from ESES-treatment, if present. We hope to present the results of this study at the end of 1995.", "To establish efficacy of a coordinated multidisciplinary rehabilitation service for severe head injury, provided at Hunters Moor Regional Rehabilitation Centre.\n A quasi-experimental design to compare treatment effects between two groups. The first group received a coordinated, multidisciplinary regional rehabilitation service; the other, a single discipline approach provided by local, district hospitals. Follow-up was for 2 years postinjury.\n Fifty-six consecutive severe head injury admissions, with an identified main caregiver, referred for rehabilitation within 4 weeks of their injury.\n The Barthel index, the Functional Independence Measure (FIM), and the Newcastle Independence Assessment Form (NIAF), a newly developed, real-life, comprehensive measure. In addition, caregivers completed the General Health Questionnaire.\n The group that received coordinated multidisciplinary rehabilitation not only demonstrated significant gains throughout the study period but also maintained treatment effect after input ended. Furthermore, caregivers of this group had significantly reduced levels of distress. The comparison group, despite initial lower injury severity and shorter hospital stay, did not demonstrate equivalent gains or any posttreatment effect.\n The results show the efficacy of a comprehensive, specialist multidisciplinary regional service. There are significant implications for service provision for people with severe traumatic head injury.", "In a prospective study, 52 patients with a spontaneous supratentorial intracerebral hematoma (ICH) were randomly assigned to receive emergency surgery or conservative treatment within 48 hours after the bleed. Patients with a decreased level of consciousness and/or a severe neurological deficit were admitted to the study. The overall mortality rate at 6 months was 42%: 10 (38%) of the 26 patients in the conservative group and 12 (46%) of the 26 in the surgical group. Six (20%) of the 30 survivors at 6 months were able to conduct their activities of daily living independently: five (31%) of the 16 patients in the conservative group and one (7%) of the 14 in the operative group. These differences are not statistically significant. The mortality rate of semicomatose or stuporous patients (Glasgow Coma Scale score 7 to 10) was statistically significantly lower in the surgical group (none of the four patients) than in the conservative group (four of five patients) (p less than 0.05); however, all surviving patients in this subgroup were severely disabled. The study suggests that surgical treatment of this category of patients with ICH does not offer any definite advantage over conservative treatment. In semicomatose or stuporous patients, surgery may improve the length of survival, but the quality of life remains poor." ]

[ "11372943", "11886906", "10622478", "11514765", "6368412", "18162669", "1762007", "1592640", "9728307" ]

[ "Extramedullary fixation of 569 unstable intertrochanteric fractures: a randomized multicenter trial of the Medoff sliding plate versus three other screw-plate systems.", "Treatment of reverse oblique and transverse intertrochanteric fractures with use of an intramedullary nail or a 95 degrees screw-plate: a prospective, randomized study.", "Extramedullary fixation of 107 subtrochanteric fractures: a randomized multicenter trial of the Medoff sliding plate versus 3 other screw-plate systems.", "Prospective randomized controlled trial of an intramedullary nail versus dynamic screw and plate for intertrochanteric fractures of the femur.", "Intertrochanteric fractures: a comparison between fixation with a two-piece nail plate and Ender's nails.", "Intramedullary nailing versus fixed angle blade plating for subtrochanteric femoral fractures: a prospective randomised controlled trial.", "Treatment of intertrochanteric fractures: comparison of Ender nails and sliding screw plates.", "[The gamma-nail as a resilient alternative to the dynamic hip screw in unstable proximal femoral fractures in the elderly].", "Treatment of intertrochanteric fracture with the Gamma AP locking nail or by a compression hip screw--a randomised prospective trial." ]

[ "We compared the efficacy of the Medoff sliding plate (MSP) with 3 other screw-plate systems for fixation of unstable intertrochanteric fractures in a randomized multicenter trial of 569 elderly patients. The MSP has biaxial dynamic capacity along both the neck and the shaft of the femur unlike the other systems, which lack dynamic capacity along the shaft. 268 fractures were operated on with the MSP, and 301 with the dynamic hip screw (DHS), with or without a trochanteric stabilizing plate (DHS/TSP) or with the dynamic condylar screw (DCS). The MSP had recently been shown to the surgeons. The patients in the groups were similar as regards age, domestic situation, preinjury walking ability and type of fracture. We followed the patients clinically and radiographically for at least 1 year. There was no significant difference in walking ability at follow-up or rate of return to home. Fixation failure occurred in 18/268 fractures operated on with the MSP, in 8/238 with the DHS, in 3/49 with the DHS/TSP and in 1/14 with the DCS. The difference in the rate of fixation failure was not statistically significant when the MSP group was compared to the 3 other groups. In 14 of the 18 fixation failures in the MSP group, the biaxial dynamic capacity of the MSP had not been used due to technical errors by surgeons, unfamiliar with the new method. No selection bias was found regarding fracture types in the 2 subgroups of patients with correct or inadequate biaxial dynamization. Extramedullary fixation of unstable intertrochanteric fractures with these implants showed a low failure rate. When using the MSP, biaxial dynamization must be correctly performed.", "Intertrochanteric fractures are composed of different anatomic patterns that vary in their degree of stability following open reduction and internal fixation. A particularly unstable group is classified as AO/OTA 31-A3, with the fracture pattern described as reverse oblique or transverse. The purpose of this study was to compare the results of intramedullary fixation with those of plate fixation for these intertrochanteric fractures in elderly patients.\n Thirty-nine elderly patients with AO/OTA 31-A3 intertrochanteric fractures of the femur were randomized into two treatment groups and were followed for a minimum of one year. The nineteen patients in Group I were treated with a 95 fixed-angle screw-plate (Dynamic Condylar Screw), and the twenty patients in Group II were treated with an intramedullary nail (Proximal Femoral Nail). The treatment groups were comparable with regard to all demographic and injury variables.\n Patients treated with an intramedullary nail had shorter operative times, fewer blood transfusions, and shorter hospital stays compared with those treated with a 95 screw-plate. Implant failure and/or nonunion was noted in seven of the nineteen patients who had been treated with the 95 screw-plate. Only one of the twenty fractures that had been treated with an intramedullary nail did not heal.\n The results of our study support the use of an intramedullary nail rather than a 95 screw-plate for the fixation of reverse oblique and transverse intertrochanteric fractures in elderly patients.", "We compared the efficacy of a load-sharing device, the Medoff sliding plate (MSP), with that of 3 other load-bearing screw-plate devices for the fixation of subtrochanteric fractures in a randomized multicenter trial of 107 elderly patients. 55 fractures were operated on with the MSP, and 52 with the dynamic hip screw (DHS) with or without a trochanteric stabilizing plate (TSP) or with the dynamic condylar screw (DCS). The patient material in the groups was similar regarding age, domestic situation, preinjury walking ability and fracture types. We followed the patients clinically and radiographically for a minimum of 1 year. There was no significant difference in walking ability or return rate to the home at follow-up. Fixation failure occurred in 1/55 fractures operated on with the MSP, in 3/32 with the DHS, in 3/12 with the DCS and in 2/8 with the DHS/TSR The difference in the rate of fixation failure was statistically significant, when the MSP group was compared to the 3 load-bearing devices in the other group (1 vs 8). On the basis of this experience, we think that the load-sharing principle of the MSP, which seems to facilitate fracture impaction and stability, appears to be a good alternative in extramedullary fixation of subtrochanteric fractures.", "To compare the surgical complications and functional outcome of the Gamma nail intramedullary fixation device versus the Richards sliding hip screw and plate device in intertrochanteric femoral fractures.\n A prospective, randomised controlled clinical trial with observer blinding.\n A regional teaching hospital in the United Kingdom.\n All patients admitted from the local population with intertrochanteric fractured femurs were included. There were 400 patients entered into the study and 399 followed-up to one year or death.\n The devices were assigned by randomization to either a short-type Gamma nail (203 patients) or a Richard's-type sliding hip screw and plate (197 patients).\n The main surgical outcome measurements were fixation failure and reoperation. A functional outcome of pain, mobility status, and range of movement were assessed until one year.\n The requirement for revision in the Gamma nail group was twelve (6%); for Richard's group, eight (4%). This was not statistically different (p = 0.29; odds ratio, 1.48 [0.59-3.7]). A subcapital femoral fracture occurred in the Richard's group. Femoral shaft fractures occurred with four in the Gamma nail group (2%) and none in the Richard's group (p = 0.13). Three required revision to another implant. Lag-screw cut-out occurred in eight patients in the gamma nail group (4%) and four in the Richard's group (2%). This was not statistically significant (p = 0.37; odds ratio, 2.29 [0.6-9.0]). The development of other postoperative complications was the same in both groups. There was no difference between the two groups in terms of early or long-term functional status at one year.\n The use of an intramedullary device in the treatment of intertrochanteric femoral fractures is still associated with a higher but nonsignificant risk of postoperative complications. Routine use of the Gamma nail in this type of fracture cannot be recommended over the current standard treatment of dynamic hip screw and plate.", "The progress of 182 patients who presented with intertrochanteric fractures was followed over a six month period. Eighty-seven patients were treated using Thornton/McLaughlin nail plates and 95 were treated using Ender's intramedullary nails. Each fracture was classified according to radiological position and mechanical stability. The results show that the more unstable fractures are more likely to develop unsatisfactory results. Post operatively, the different mechanical complications have been recorded at various stages. Those fractures fixed with a nail plate tended to develop varus deformity resulting from either bony collapse around the implant or implant failure, whereas those fixed with Ender's nails did not develop deformity at the fracture site but encountered distal migration of the nails at the knee. The use of a classification system in predicting post operative mechanical complications is considered, and the comparative merits and disadvantages of the two fixation systems is discussed, with suggestions for improvement in operative technique.", "To compare closed intramedullary nailing to open reduction and internal fixation using a fixed angle blade plate for the management of subtrochanteric femoral fractures.\n 58 patients were equally randomised to undergo either an intramedullary nailing (IN) or fixed angle blade plating (BP).\n There were no significant differences between the 2 groups with regard to age, time to surgery, operating time, receipt of blood transfusions, duration of hospital stay, or fracture classification. The revision rate was 28% (8/29) in the BP group and none in the IN group; the difference was statistically significant.\n Internal fixation using a fixed angle blade plate for subtrochanteric femoral fractures has higher implant failure and revision rates, compared to closed intramedullary nailing.", "The results of two fixation devices for the treatment of intertrochanteric fractures were compared in 220 patients--163 women and 57 men with a mean age of 81 +/- 10 years. One hundred and one patients were randomized to Ender nailing and 119 to fixation with a sliding screw plate (SSP). The two treatment groups were equal with respect to important preinjury variables. The two methods did not differ in operating time or perioperative blood loss. The proportions of good reduction of the fractures and of good positioning of the internal fixation devices were equal in the two groups. But the complication rate and the reoperation rate were more than twice as high in the Ender group than in the SSP group. The outcome at 1-year follow-up was approximately equal in the two groups.", "In a prospective randomised trial between September 1989 and June 1990 one hundred patients with per- and subtrochanteric fractures were consecutively treated by gamma-nail or DHS. The average age of both groups was about 80 years. The operation time for gamma-nailing was longer than for DHS implantation and also the postoperative blood loss was higher in the gamma-nail group. We found no difference of intraoperative blood loss, of perioperative lethality and in duration of hospital care. 90% of gamma-nail patients and 80% of DHS patients were successfully able to walk four days after operation with full weight bearing on the operated limb. Three patients in the DHS group with unstable fractures got cranial perforation of the cephalic screw mobilisation. Five patients of the gamma-nail group were reoperated, one case because of missed distal locking, one because of cranial perforation of the cephalic screw after varus dislocation of the proximal fragment. One patient suffered intraoperatively a proximal femur shaft fracture which was corrected during operation. In one case a wound hematoma was evacuated, an other patient needed secondary wound closure. Despite technical imperfection of implant and instruments, we conclude that the gamma-nail allows a very high percentage early and full weight bearing immediately after operation. So we consider that in the treatment of unstable pertrochanteric fractures of geriatric patients, the gamma-nail has proven to be more efficient than the DHS.", "The Gamma AP (Asia-Pacific) locking nail (GAPN) is a modification of the standard Gamma locking nail made especially for use in Oriental patients. We made a randomised prospective comparison of the compression hip screw (CHS) and the Gamma AP locking nail for the internal fixation of 60 intertrochanteric fractures of the hip in elderly patients by comparing perioperative details and analysing the radiographic and clinical results. The operation time for the GAPN group was shorter than for the CHS group and the intraoperative blood loss was lower. The Gamma AP nail enabled earlier mobilisation. We found no significant difference in the time to union and the length of sliding of the lag screw between the two groups. The decrease in the neck shaft angle in the Gamma nail group was significantly smaller than in the CHS patients. There were no significant mechanical complications, such as fracture of the femoral shaft or failure of fixation in the Gamma nail group. On the basis of our observations we conclude that the Gamma AP locking nail is more efficient than the CHS in the treatment of intertrochanteric fractures in geriatric patients." ]

[ "16968847", "17846935", "9821420", "1912887", "12728089", "15930204", "19671372", "11159657", "10819344" ]

[ "Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial.", "Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16.", "A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children.", "Acute red ear in children: controlled trial of non-antibiotic treatment in general practice.", "Antibiotic treatment of acute otorrhea through tympanostomy tube: randomized double-blind placebo-controlled study with daily follow-up.", "Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment.", "A double-blind randomised placebo-controlled trial of topical intranasal corticosteroids in 4- to 11-year-old children with persistent bilateral otitis media with effusion in primary care.", "Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media.", "Five vs. ten days of antibiotic therapy for acute otitis media in young children." ]

[ "Acute otitis media (AOM) is the most common diagnosis for which antibiotics are prescribed for children. Previous trials that have evaluated a \"wait-and-see prescription\" (WASP) for antibiotics, with which parents are asked not to fill the prescription unless the child either is not better or is worse in 48 hours, have excluded children with severe AOM. None of these trials were conducted in an emergency department.\n To determine whether treatment of AOM using a WASP significantly reduces use of antibiotics compared with a \"standard prescription\" (SP) and to evaluate the effects of this intervention on clinical symptoms and adverse outcomes related to antibiotic use.\n A randomized controlled trial conducted between July 12, 2004, and July 11, 2005. Children with AOM aged 6 months to 12 years seen in an emergency department were randomly assigned to receive either a WASP or an SP. All patients received ibuprofen and otic analgesic drops for use at home. A research assistant, blinded to group assignment, conducted structured phone interviews 4 to 6, 11 to 14, and 30 to 40 days after enrollment to determine outcomes.\n Filling of the antibiotic prescription and clinical course.\n Overall, 283 patients were randomized either to the WASP group (n = 138) or the SP group (n = 145). Substantially more parents in the WASP group did not fill the antibiotic prescription (62% vs 13%; P<.001). There was no statistically significant difference between the groups in the frequency of subsequent fever, otalgia, or unscheduled visits for medical care. Within the WASP group, both fever (relative risk [RR], 2.95; 95% confidence interval [CI], 1.75 - 4.99; P<.001) and otalgia (RR, 1.62; 95% CI, 1.26 - 2.03; P<.001) were associated with filling the prescription.\n The WASP approach substantially reduced unnecessary use of antibiotics in children with AOM seen in an emergency department and may be an alternative to routine use of antimicrobials for treatment of such children.\n clinicaltrials.gov Identifier: NCT00250900.", "To study the clinical recovery from acute otitis media (AOM) in children, 2-16 years of age, managed with or without treatment with phenoxymethylpenicillin (PcV).\n An open, prospective randomized trial. Children aged between 2 and 16 years, presenting with one- or double-sided AOM (without perforation) with symptom duration of less than four days, were included. The children were randomized to PcV for five days or to no primary antibiotic treatment. A health score and compliance were registered on a daily basis for seven days.\n A total of 32 health centres and 72 GPs in south-east Sweden. Subjects. Children aged 2-16 presenting with earache.\n Recovery time, symptom duration, frequency of complications (up to three months) and consumption of healthcare services independent of treatment with or without antibiotics.\n A total of 179 patients carried out the trial; 92 were randomized to PcV, 87 to no primary antibiotic treatment. The median recovery time was four days in both groups. Patients who received PcV had less pain (p <0.001) and used fewer analgesics. There were no significant differences in the number of middle-ear effusions or perforations at the final control after three months. Children randomized to PcV treatment consulted less (p <0.001) during the first seven days.\n Our investigation supports that PcV treatment of AOM does not affect the recovery time or complication rates. PcV provided some symptomatic benefit in the treatment of AOM in otherwise healthy children, aged 2-16 years.", "All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure.\n In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period.\n Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008).\n When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM.", "To examine the efficacy and safety of conservative management of mild otitis media (\"the acute red ear\") in children.\n Double blind placebo controlled trial.\n 17 group general practices (48 general practitioners) in Southampton, Bristol, and Portsmouth.\n 232 children aged 3-10 years with acute earache and at least one abnormal eardrum (114 allocated to receive antibiotic, 118 placebo).\n Amoxycillin 125 mg three times a day for seven days or matching placebo; 100 ml paracetamol 120 mg/5 ml.\n Diary records of pain and crying, use of analgesic, eardrum signs, failure of treatment, tympanometry at one and three months, recurrence rate, and ear, nose, and throat referral rate over one year.\n Treatment failure was eight times more likely in the placebo than the antibiotic group (14.4% v 1.7%, odds ratio 8.21, 95% confidence interval 1.94 to 34.7). Children in the placebo group showed a significantly higher incidence of fever on the day after entry (20% v 8%, p less than 0.05), mean analgesic consumption (0.36 ml/h v 0.21 ml/h, difference 0.14, 95% confidence interval 0.07 to 0.23; p = 0.0022), mean duration of crying (1.44 days v 0.50 days, 0.94; 0.50 to 1.38; p less than 0.001), and mean absence from school (1.96 days v 0.52 days, 1.45; 0.46 to 2.42; p = 0.0132). Differences in recorded pain were not significant. The prevalence of middle ear effusion at one or three months, as defined by tympanometry, was not significantly different, nor was there any difference in recurrence rate or in ear, nose, and throat referral rate in the follow up year. No characteristics could be identified which predicted an adverse outcome.\n Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy.", "The role of routine antimicrobial treatment of acute middle-ear infections is under debate, because the efficacy of antimicrobials in the resolution of middle-ear fluid has not been unambiguously proven. Acute tube otorrhea is regarded as evidence of acute otitis media, and for methodologic reasons it was chosen to provide objectivity for diagnostics and outcome assessment. The objective of this study was to assess whether amoxicillin-clavulanate accelerates the resolution of acute tube otorrhea.\n Randomized, double-blind, placebo-controlled study in outpatient setting.\n Volunteer sample of basically healthy 6- to 72-month-old children with a tympanostomy tube. Eligibility required having acute tube otorrhea of <48 hours' of duration and no prior treatment within the last 2 weeks. The mean age of the participants was 25 months; they had a history of 3 episodes of acute otitis media (median), and 99% had manifestations of a concomitant respiratory infection. Of 79 randomized patients, 7 were withdrawn because of adverse events; 66 patients completed the study.\n Amoxicillin-clavulanate (N = 34; 45 mg/kg/d) or matching placebo (N = 32) for 7 days and daily suction of middle-ear fluid through tympanostomy tube.\n Duration of acute tube otorrhea and duration of bacterial growth in middle-ear fluid.\n The median duration of tube otorrhea was significantly shorter in amoxicillin-clavulanate than in the placebo group (3 vs 8 days). At the end of the 7-day medication period, tube otorrhea was resolved in 28 of 34 children receiving amoxicillin-clavulanate compared with 13 of 32 children on placebo (treatment-control difference 41%; 95% confidence interval, 20%-63%; number needed to treat, 2.4). The median duration of bacterial growth in middle-ear fluid was shorter in amoxicillin-clavulanate than in the placebo group (1 vs 8 days).\n Oral antibiotic treatment significantly accelerates the resolution of acute tube otorrhea by reducing bacterial growth in middle-ear fluid.", "The widespread use of antibiotics for treatment of acute otitis media (AOM) has resulted in the emergence of multidrug-resistant pathogens that are difficult to treat. However, it has been shown that most children with nonsevere AOM recover without ABX. The objective of this study was to evaluate the safety, efficacy, acceptability, and costs of a non-ABX intervention for children with nonsevere AOM.\n Children 6 months to 12 years old with AOM were screened by using a novel AOM-severity screening index. Parents of children with nonsevere AOM received an educational intervention, and their children were randomized to receive either immediate antibiotics (ABX; amoxicillin plus symptom medication) or watchful waiting (WW; symptom medication only). The investigators, but not the parents, were blinded to enrollment status. Primary outcomes included parent satisfaction with AOM care, resolution of symptoms, AOM failure/recurrence, and nasopharyngeal carriage of Streptococcus pneumoniae strains resistant to ABX. Secondary outcomes included medication-related adverse events, serious adverse events, unanticipated AOM-related office and emergency department visits and telephone calls, the child's absence from day care or school resulting from AOM, the parent's absence from school or work because of their child's AOM, and costs of treatment. Subjects were defined as failing (days 0-12) or recurring (days 13-30) if they experienced a higher AOM-severity score on reexamination.\n A total of 223 subjects were recruited: 73% were nonwhite, 57% were <2 years old, 47% attended day care, 82% had experienced prior AOM, and 83% had not been fully immunized with heptavalent pneumococcal vaccine. One hundred twelve were randomized to ABX, and 111 were randomized to WW. Ninety-four percent of the subjects were followed to the 30-day end point. Parent satisfaction with AOM care was not different between the 2 treatment groups at either day 12 or 30. Compared with WW, symptom scores on days 1 to 10 resolved faster in subjects treated with immediate ABX. At day 12, among the immediate-ABX group, 69% of tympanic membranes and 25% of tympanograms were normal, compared with 51% of normal tympanic membranes and 10% of normal tympanograms in the WW group. Parents of children in the ABX group gave their children fewer doses of pain medication than did parents of children in the WW group. Subjects in the ABX group experienced 16% fewer failures than subjects in the WW group. Of the children in the WW group, 66% completed the study without needing ABX. Immediate ABX resulted in eradication of S pneumoniae carriage in the majority of children, but S pneumoniae strains cultured from children in the ABX group at day 12 were more likely to be multidrug-resistant than strains from children in the WW group. More ABX-related adverse events were noted in the ABX group, compared with the WW group. No serious AOM-related adverse events were observed in either group. Office and emergency department visits, phone calls, and days of work/school missed were not different between groups. Prescriptions for ABX were reduced by 73% in the WW group compared with the ABX group. Costs of ABX averaged $47.41 per subject in the ABX group and $11.43 in the WW group.\n Sixty-six percent of subjects in the WW group completed the study without ABX. Parent satisfaction was the same between groups regardless of treatment. Compared with WW, immediate ABX treatment was associated with decreased numbers of treatment failures and improved symptom control but increased ABX-related adverse events and a higher percent carriage of multidrug-resistant S pneumoniae strains in the nasopharynx at the day-12 visit. Key factors in implementing a WW strategy were (a) a method to classify AOM severity; (b) parent education; (c) management of AOM symptoms; (d) access to follow-up care; and (e) use of an effective ABX regimen, when needed. When these caveats are observed, WW may be an acceptable alternative to immediate ABX for some children with nonsevere AOM.", "To determine the clinical effectiveness and cost-effectiveness of topical mometasone in children with bilateral otitis media with effusion (OME).\n A double-blind randomised placebo-controlled trial with an intention to treat analysis; the 10.6% of patients lost to follow-up at 1 month were censored in the analysis.\n 76 Medical Research Council General Practice Research Framework practices throughout the UK between 2004 and 2007.\n A sample of 217 children aged 4-11 years was selected from those presenting to their GP with one or more episodes of otitis media or ear-related problems in the previous 12 months whom the research nurse confirmed had bilateral glue ear using microtympanometry (B B or B C2 types using a modified Jerger classification) at randomisation.\n Mometasone 50 micrograms in each nostril or placebo spray once daily for 3 months.\n The primary outcome was the proportions of children cleared of OME assessed by tympanometry at 1 month. Secondary outcomes included clearance at 3 months and 9 months; adverse events; OM8-30 scores (a functional health status responsive disease-specific measure); hearing loss; days with otalgia; cost-effectiveness; and health utilities.\n Of the topical steroid group, 40.6% (39/96) demonstrated tympanometric clearance (C1 or A type) in one or both ears at 1 month, compared with 44.9% (44/98) of the placebo group. The absolute risk reduction at 1 month was -4.3% (95% CI -18.05% to 9.26%); the odds ratio (OR) was 0.84 (95% CI 0.48 to 1.48). Four covariates were pre-specified for inclusion in logistic regression analysis: age as a continuous variable (p = 0.94), season (p = 0.70), atopy (p = 0.61) and clinical severity (p = 0.006). The adjusted OR (AOR) at 1 month for the main outcome was 0.93 (95% CI 0.50 to 1.75). Secondary analysis at 3 months showed 58.1% of the steroid group had resolved and 52.3% of the placebo group, AOR 1.45 (95% CI 0.74 to 2.84). At 9 months 55.6% of the treated group remained clear in at least one ear and 65.3% of the placebo group, AOR 0.82 (95% CI 0.39 to 1.75). Adverse events (although relatively minor) occurred in 7-22% of children and included nasal stinging, epistaxis, dry throat and cough. The OM8-30 scores (p = 0.55) reported hearing difficulty (p = 0.08), and days with otalgia (p = 0.46) were not significantly different between groups at 3 months. The economic evaluation found the active treatment arm to be dominated by placebo, accruing slightly (but not significantly) higher costs and fewer quality-adjusted life-years (QALYs), with a 24.2% probability that topical steroids are a cost-effective use of NHS resources at a ceiling ratio of 20,000 pounds per QALY gained.\n Use of topical intranasal corticosteroids is very unlikely to be a clinically effective treatment for OME (glue ear) in the primary care setting.\n Current Controlled Trials ISRCTN38988331.", "To compare immediate with delayed prescribing of antibiotics for acute otitis media.\n Open randomised controlled trial. Setting: General practices in south west England.\n 315 children aged between 6 months and 10 years presenting with acute otitis media.\n Two treatment strategies, supported by standardised advice sheets-immediate antibiotics or delayed antibiotics (antibiotic prescription to be collected at parents' discretion after 72 hours if child still not improving).\n Symptom resolution, absence from school or nursery, paracetamol consumption.\n On average, symptoms resolved after 3 days. Children prescribed antibiotics immediately had shorter illness (-1.1 days (95% confidence interval -0.54 to -1.48)), fewer nights disturbed (-0.72 (-0.30 to -1.13)), and slightly less paracetamol consumption (-0.52 spoons/day (-0.26 to -0.79)). There was no difference in school absence or pain or distress scores since benefits of antibiotics occurred mainly after the first 24 hours-when distress was less severe. Parents of 36/150 of the children given delayed prescriptions used antibiotics, and 77% were very satisfied. Fewer children in the delayed group had diarrhoea (14/150 (9%) v 25/135 (19%), chi(2)=5.2, P=0.02). Fewer parents in the delayed group believed in the effectiveness of antibiotics and in the need to see the doctor with future episodes.\n Immediate antibiotic prescription provided symptomatic benefit mainly after first 24 hours, when symptoms were already resolving. For children who are not very unwell systemically, a wait and see approach seems feasible and acceptable to parents and should substantially reduce the use of antibiotics for acute otitis media.", "Many publications in recent years have argued in favor of shortened therapy for acute otitis media. However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years.\n In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period.\n Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group. In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009). The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs. 81.5%). Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68).\n The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol." ]

[ "21829969", "19434268", "3781700", "15572814", "6889154", "17567657", "11533321", "9063425", "4190002" ]

[ "Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study.", "Management for the children with otitis media with effusion in the tertiary hospital.", "Possibility of interaction among antibiotics and mucolytics in children.", "Comparison of two antibiotic regimens in the empirical treatment of severe childhood pneumonia.", "Prophylaxis of otitis media in asthmatic children.", "Comparison of oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children (PIVOT trial): a multicentre pragmatic randomised controlled equivalence trial.", "A community intervention trial to promote judicious antibiotic use and reduce penicillin-resistant Streptococcus pneumoniae carriage in children.", "Is an antihistamine-decongestant combination effective in temporarily relieving symptoms of the common cold in preschool children?", "Treatment of acute otitis media: a controlled study of 142 children." ]

[ "To compare clinical response to initial empiric treatment with oxacillin plus ceftriaxone and amoxicillin plus clavulanic acid in hospitalized children diagnosed with very severe community-acquired pneumonia (CAP).\n A prospective randomized clinical study was conducted among children 2 months to 5 years old with a diagnosis of very severe CAP in the pediatric ward of São Paulo State University Hospital in Botucatu, São Paulo, Brazil, from April 2007 to May 2008. Patients were randomly divided into two groups by type of treatment: an oxacillin/ceftriaxone group (OCG, n = 48) and an amoxicillin/clavulanic acid group (ACG, n = 56). Analyzed outcomes were: time to clinical improvement (fever and tachypnea), time on oxygen therapy, length of stay in hospital, need to widen antimicrobial spectrum, and complications (including pleural effusion).\n The two groups did not differ statistically for age, sex, symptom duration before admission, or previous antibiotic treatment. Time to improve tachypnea was less among ACG patients than OCG patients (4.8 ± 2.2 versus 5.8 ± 2.4 days respectively; P = 0.028), as was length of hospital stay (11.0 ± 6.2 versus 14.4 ± 4.5 days respectively; P = 0.002). There were no statistically significant differences between the two groups for fever improvement time, time on oxygen therapy, need to widen antimicrobial spectrum, or frequency of pleural effusion.\n Both treatment plans are effective in treating very severe CAP in 2-month-to 5-year-old hospitalized children. The only analyzed outcome that favored amoxicillin/clavulanic acid treatment was time required to improve tachypnea.\n ClinicalTrials.gov ID: NCT01166932.", "Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.\n Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.\n Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).\n In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.", "A controlled clinical trial in children with acute infections of the lower respiratory tract was carried out to see whether or not treatment with ambroxol could bring about faster and better results. One hundred twenty children with acute lower respiratory tract infections were all given antibiotics plus, at random, either ambroxol (1.5-2.0 mg/kg body weight orally) or a placebo. The duration of the trial was ten days. All the patients in both groups were cured clinically. However, remission of the cough, of the chest pathological signs, as well as the improvement of the lung radiographical pictures were significantly more rapid in children treated with ambroxol than in those who received the antibiotic alone. Ambroxol was tolerated perfectly by all the children.", "The diagnosis and the treatment of community-acquired severe pneumonia is still a serious child health problem in developing countries. The aim of this study is to evaluate the effectiveness of two different antibiotic regimens in the empirical treatment of severe childhood pneumonia.\n We enrolled 97 infants (aged 2-24 months) with severe community-acquired pneumonia in a randomized-controlled trial of 10 days of treatment with penicillin G+chloramphenicol (n:46) or ceftriaxone (n:51). We evaluated the effectiveness of treatments with symptoms and some laboratory tests during and at the end of the study.\n The cure rates were similar in both groups and the antibiotic regimens in all patients were found effective (P< 0.001). The number of nurse rounds was much more in penicillin plus chloramphenicol group than ceftriaxone group.\n Both penicillin G plus chloramphenicol and ceftriaxone are effective in the empirical treatment of severe community pneumonia of young children. In spite of more nurse visits for antibiotic treatment, penicillin G+ chloramphenicol combination may be a cheaper alternative to ceftriaxone in the treatment of childhood pneumonia.", "Seventy-two asthmatic children with recurrent otitis media were studied over a 2-year interval. They were randomly divided to receive either (1) no routine medication, (2) antihistamines whenever nasally congested, (3) daily sulfisoxazole at 500 mg twice a day, (4) pneumococcal immunization and (5) both pneumococcal vaccine and 500 mg sulfisoxazole twice daily. There was no apparent benefit in the antihistamine group. There was a mean yearly reduction in otitis media of 75% in the sulfisoxazole group, 38% in the pneumococcal vaccine group and 90% in the group treated with both agents. The latter group also had a 56% reduction in frequency of acute asthmatic attacks and a 90% decrease in hospitalizations associated with otitis media. In conclusion the use of sulfisoxazole and pneumococcal vaccine appears efficacious for management of asthmatic children with recurrent otitis media.", "To ascertain whether therapeutic equivalence exists for the treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes.\n A multicentre pragmatic randomised controlled non-blinded equivalence trial was undertaken in eight paediatric centres in England (district general and tertiary hospitals). Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. 246 children who required admission to hospital and had fever, respiratory symptoms or signs and radiologically confirmed pneumonia were included in the study. Exclusion criteria were wheeze, oxygen saturations <85% in air, shock requiring >20 ml/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age <6 months. The patients were randomised to receive oral amoxicillin for 7 days (n = 126) or IV benzyl penicillin (n = 120). Children in the IV group were changed to oral amoxicillin after a median of six IV doses and received 7 days of antibiotics in total. The predefined primary outcome measure was time for the temperature to be <38 degrees C for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness.\n Oral amoxicillin and IV benzyl penicillin were shown to be equivalent. Median time for temperature to settle was 1.3 days in both groups (p<0.001 for equivalence). Three children in the oral group were changed to IV antibiotics and seven children in the IV group were changed to different IV antibiotics. Median time to complete resolution of symptoms was 9 days in both groups.\n Oral amoxicillin is effective for most children admitted to hospital with pneumonia (all but those with the most severe disease who were excluded from this study). Prior to this study, the British Thoracic Society guidelines on childhood pneumonia could not draw on evidence to address this issue. This will spare children and their families the trauma and pain of cannulation, and children will spend less time in hospital.", "Inappropriate use of antibiotics is common in primary care, and effective interventions are needed to promote judicious antibiotic use and reduce antibiotic resistance. The objective of this study was to assess the impact of parent and clinician education on pediatric antibiotic prescribing and carriage of penicillin-nonsusceptible Streptococcus pneumoniae in child care facilities.\n A nonrandomized, controlled, community intervention trial was conducted in northern Wisconsin Clinicians. Clinic staff received educational materials and small-group presentations; materials were distributed to parents through clinics, child care facilities, and community organizations. Prescribing data were analyzed for 151 clinicians who provided primary pediatric care; nasopharyngeal carriage of penicillin-nonsusceptible S pneumoniae was assessed for 664 children in the baseline period (January-June 1997) and for 472 children in the postintervention period (January-June 1998).\n The median number of solid antibiotic prescriptions per clinician declined 19% in the intervention region and 8% in the control region. The median number of liquid antibiotic prescriptions per clinician declined 11% in the intervention region, compared with an increase of 12% in the control region. Retail antibiotic sales declined in the intervention region but not in the control region. Among participating children in child care facilities, there were no significant differences in antibiotic use or penicillin-nonsusceptible S pneumoniae colonization between the intervention and control regions.\n A multifaceted educational program for clinicians and parents led to community-wide reductions in antibiotic prescribing, but in child care facilities, there was no apparent impact on judicious antibiotic use or colonization with drug-resistant S pneumoniae. Longer follow-up time or greater reductions in antibiotic use may be required to identify changes in the pneumococcal susceptibility.", "To determine whether an antihistamine-decongestant combination (ADC) is superior to placebo in temporarily relieving symptoms of upper respiratory tract infection (URI) in preschool children.\n Randomized, double-blind, placebo-controlled trial.\n Four pediatric offices in the Seattle, Wash, area.\n Children 6 months through 5 years of age with a URI of less than 7 days' duration.\n Children were randomly assigned to receive an ADC (brompheniramine maleate-phenylpropanolamine hydrochloride) or placebo as needed for URI symptoms. Two hours after each dose of study medication, changes in the child's runny nose, nasal congestion, cough, and sleep status were assessed by means of a standardized questionnaire.\n A total of 175 responses were recorded for 59 patients. There were no statistically significant differences in symptom improvement between the ADC and the placebo group (runny nose, p = 0.48; nasal congestion, p = 0.94; cough, p = 0.66). However, the proportion of children asleep 2 hours after receiving the ADC was significantly higher than the proportion receiving placebo (46.6% vs 26.5%; p = 0.01). Results were unchanged after control for the correlated nature of repeated responses, age, symptom duration, use of acetaminophen, time that the medication was given, and parental desire for medication.\n The ADC was equivalent to placebo in providing temporary relief of URI symptoms in preschool children. However, the ADC did have significantly greater sedative effects than did placebo.", "Results of the use of ampicillin, penicillin G and symptomatic therapy in the treatment of acute otitis media in 142 children were compared. Antibiotic therapy conveyed significant benefit. No major differences were observed between penicillin and ampicillin, except in the age group under 3 years where ampicillin was associated with the best results. Ampicillin appears to be the drug of choice. Its superiority over symptomatic therapy was statistically significant. Long-term sequelae were not observed in any of the three treatment groups. The relative merits of erythromycin and ampicillin require further study." ]

[ "9212478", "14742379", "12791434", "8665549", "7644238", "9313274", "14594516", "8537695", "11498314" ]

[ "Comparison of oral controlled-release morphine with transdermal fentanyl in terminal cancer pain.", "A placebo-controlled randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain.", "Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain--results of a randomized double-blinded, placebo-controlled trial.", "Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo.", "Analgesic efficacy and safety of single-dose intramuscular ketorolac for postoperative pain management in children following tonsillectomy.", "Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation.", "Comparison of TTS-fentanyl with sustained-release oral morphine in the treatment of patients not using opioids for mild-to-moderate pain.", "Long-term intraspinal infusions of opioids in the treatment of neuropathic pain.", "Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery." ]

[ "Controlled-release morphine (MST) given twice daily provides a simpler and more convenient treatment regimen than 4-hourly opioid administration for the control of cancer pain. Recently, a new formulation of transdermal fentanyl (TDF) has been developed which provides a new route for the treatment of cancer pain. The present study was designed to compare the analgesic efficacy, safety and adverse effects of MST and TDF in the management of chronic cancer pain.\n In this open, comparative and randomized study, patients were treated with oral morphine hydrochloride immediate-release (MHIR) in the stabilization phase and then the prescription was switched to MST or TDF for 14 days in the treatment phase. Oral MHIR was provided as rescue medication for breakthrough pain. Assessments of the pain intensity, pain frequency, degree of pain improvement, profile of mood states, quality of sleep, activity status and adverse effects were performed before and after the stabilization phase and before and after the treatment phase.\n Forty of 47 cancer patients completed the study with 20 patients in each group. There were significant (p < 0.05) improvements in pain intensity, pain frequency, mood states and quality of sleep in both groups before and after treatment, while improvement in the activity status was not significant. No specific adverse effects were encountered except for drowsiness which occurred in 6 patients treated with MST and 5 treated with TDF (p < 0.05). Insomnia was significantly improved (p < 0.05) with both regimens compared with that in the period before treatment. There were no significant differences between the two study groups in analgesic efficacy or adverse effects.\n These results suggest that TDF and MSt are safe and effective analgesics for the management of chronic cancer pain. However, TDF provides a simpler and more convenient treatment for those patients with severe nausea, vomiting or dysphagia.", "In the present study we investigated the effect of the N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine (30 mg/d) on the intensity of chronic phantom limb pain (PLP) and cortical reorganization. In 8 patients with chronic PLP, memantine was tested in a placebo-controlled double-blinded crossover trial of 4 wk duration per trial. The intensity of PLP was rated hourly by the patients on a visual analog scale during baseline and both treatment periods. At the same time points, the functional organization of the primary somatosensory cortex (SI) was determined by neuromagnetic source imaging. In comparison to baseline and placebo, the NMDA receptor antagonist had no effect on the intensity of chronic PLP. In none of the periods were significant changes in the functional organization of SI observed. Although the conclusions regarding the clinical effect are limited because of the small sample size, the data indicate that in the studied dosage the NMDA receptor antagonist memantine is ineffective in the treatment of chronic PLP and is also ineffective for the reduction of associated neural plasticity in the primary SI.\n NMDA receptors play a substantial role in central nervous system changes underlying neuropathic pain. In a placebo-controlled double-blinded study we tested the effect of 30 mg memantine on chronic phantom limb pain and pain-associated cortical reorganization.", "Phantom limb pain (PLP) associated neuroplastic changes are partly mediated by excitatory amino acids at NMDA receptor sites. This study was undertaken to deduce if NMDA-receptor antagonists may be effective in patients with chronic PLP. Therefore a four week double-blinded, randomized placebo-controlled trial was performed to evaluate the efficacy of 30 mg memantine/day, an orally administrable NMDA receptor antagonist.Thirty-six patients, 18 per group, with a history of at least 12 months PLP and an average pain of at least 4 on the 11-point numeric rating scale (NRS) were enrolled. The patients completed a standardized questionnaire before the trial. PLP intensity and the level of eight complaints were assessed during the trial. Number needed to treat (NNT) was calculated based on the average PLP during the 3rd week (steady state). In both groups, PLP declined significantly in comparison with the baseline (verum: 5.1 (+/-2.1) to 3,8 (+/-2,3), placebo from 5.1 (+/-2.0) to 3.2 (+/-1,46) NRS) without a re-rising of the PLP during the washout period. Mean pain relief was 47% in the memantine group (10 patients reported more than 50% relief), 40% in the placebo group (6>50%): NNT were 4.5 (KI: 2.1-10.6). Analysis of covariance demonstrated a significant impact only on the prior PLP intensity, but no treatment effect. Two patients have demonstrated long-term pain relief under memantine until now (16 months). The total number of slight adverse events were comparable in both groups, but the overall number of severe events was higher in the memantine group (P<0.05). This trial failed to demonstrate a significant clinical benefit of the NMDA-receptor antagonist memantine in chronic PLP. The administration of a higher dosage is probably not tolerable.", "NMDA antagonists and opioids relieve experimentally produced hyperalgesia in animals and humans, presumably by attenuating a heightened central nervous system response to afferent input. A few small studies in patients have suggested that intravenous boluses or rapid infusions of the N-methyl-D-aspartate (NMDA) antagonist ketamine relieve some neuropathic pains but also produce disturbances of cognition and mood. In a randomized, double-blind, crossover trial, we treated eight patients with chronic posttraumatic pain and widespread mechanical allodynia with 2-h intravenous infusions of the NMDA antagonist ketamine (mean dose, 58 mg), the opioid mu-receptor agonist alfentanil (mean dose, 11 mg), and placebo. The patients were selected because extensive sensory testing suggested that altered central processing contributed to their symptoms. The slow rate of drug infusion was chosen to see if pain relief would precede dose-limiting side effects. Means of the peak effect scores achieved during the 2-h infusion were for pain relief: ketamine, 65%, alfentanil, 46%, and placebo, 22% (p < 0.01 for ketamine and p = 0.08 for alfentanil, each compared to placebo); and for relief of allodynia: ketamine, 71%, alfentanil, 57%, and placebo, 21% (p < 0.01 for both ketamine and alfentanil). Appreciable symptomatic relief developed only after the onset of unpleasant drug side effects. After the infusion was stopped, pain relief disappeared before the side effects resolved. We conclude that NMDA antagonists may have promise for the treatment of neuropathic pain, but strategies are needed to improve their therapeutic ratio, such as intrathecal administration or systemic treatment with more selective drugs.", "The efficacy of ketorolac, a non-steroidal anti-inflammatory drug, in the management of moderate to severe pain in adults, has led us to conduct a trial of this analgesic in children following tonsillectomy. Children were randomized to receive intramuscular (i.m.) ketorolac (1 mg/kg, EXP group, n = 45) or saline (CTL group, n = 42) at the completion of surgery. Intravenous (i.v.) fentanyl (0.5 micrograms/kg/dose) was administered in repeated doses postoperatively. Pain intensity was measured using both the Oucher and the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) to allow for comparison between self-report and behavioral measures of pain intensity. Severity of postoperative bleeding was measured using a 4-point rating scale. The EXP group had a significant reduction in total fentanyl dose (mean: 35.9 micrograms) compared to the CTL group (mean: 48.3 micrograms, t = -2.21, P < 0.03). There was a statistically significant decrease in pre-fentanyl CHEOPS scores in the Post-Anesthesia Care Unit (PACU) in the ketorolac group (F (2, 30) = 5.34, P < 0.01), but not in the saline group (F (2.24) = 2.46, P > 0.05). In the first hour postoperatively, the CHEOPS demonstrated significant decreases in pain intensity scores in response to opioids, in both groups. In the PACU, children were unable to provide a self-report of pain intensity potentially due to a variety of factors (e.g., emergence delirium, agitation, excitement, sedation, and/or pain). However, during the remainder of the postoperative stay, the photographic scale of the Oucher was a more valid measure of pain intensity than the CHEOPS.(ABSTRACT TRUNCATED AT 250 WORDS)", "A total of 119 bone marrow transplant patients suffering from oral mucositis pain were enrolled in a randomized, double-blind, parallel-group trial comparing the efficacy of patient-controlled analgesia with morphine, hydromorphone and sufentanil. Patient ratings of pain and side-effects on visual analog scales were gathered daily from the start of patient-controlled analgesia (PCA) therapy until the discontinuation of opioid treatment either because of resolution of oral mucositis pain, intolerable side-effects, inadequate pain control, or complications related to transplantation. Of the 119 enrolled subjects, 100 met the evaluable criteria of developing oral mucositis and remaining on the study for at least 2 days. Multivariate analysis of the outcome measures indicated that the analgesia achieved in all three opioid groups was nearly equivalent, while measures of side-effects, especially for the combination of sedation, sleep and mood disturbances, were statistically lower in the morphine group than in hydromorphone or sufentanil groups. Patients in the hydromorphone group exhibited the most variability in pain control. Event analysis also indicated significant differences in time to treatment failure between the three groups, with the morphine arm exhibiting clear superiority. The proportion of patients discontinued because of inadequate pain relief was much higher in the sufentanil group (7/36) as compared to the hydromorphone (0/34) or the morphine group (1/30). The daily opioid consumption pattern showed a continual dose escalation during the first week of therapy for all groups, coincident with worsening mucositis. Morphine consumption reached a plateau by day 5, whereas hydromorphone and sufentanil consumption continued to rise until days 7 and 9, respectively. Sufentanil dose requirement increased by approximately 10-fold compared to morphine and hydromorphone, whose requirements increased only 5-fold, suggesting the possibility of development of acute pharmacological tolerance in some patients with this phenylpiperidine opioid. This study provides support for the recommendation that morphine is the opioid of first choice when patient-controlled analgesia is employed for the treatment of severe oropharyngeal pain in bone marrow transplantation (BMT) patients.", "This randomised, multicentre, direct open comparative trial evaluated the efficacy, treatment convenience, tolerability and safety aspects of transdermal therapeutic system (TTS)-fentanyl and sustained-release oral morphine (SRM) in both opioid-naïve patients with moderate-to-severe cancer-related pain and in patients who had already been using opioids for mild-to-moderate pain. The two treatment groups were run in parallel. Special attention was paid to constipation, nausea/vomiting, drowsiness and respiratory depression.\n The 131 enrolled patients started the 4-week treatment at low doses of opioid (25 microg/h TTS-fentanyl for 3 days or 30 mg SRM every 12 h) and were individually titrated. Tolerability, efficacy and safety were assessed throughout the study period. Frequency of constipation was the primary study variable and accordingly the study was powered for this. Both patients and investigators made a global treatment evaluation.\n TTS-fentanyl and SRM were shown to be equally effective. Pain control and sleep quality improved with both treatments. None of the patients developed respiratory depression. Statistically significantly more patients in the SRM treatment group discontinued the trial prematurely (59% vs 27%; p < 0.001), particularly due to adverse events (36% vs 4%; p < 0.001). Fewer patients in the TTS-fentanyl than in the SRM treatment group reported constipation during the trial. This finding was statistically significant after 1 week of treatment (27% vs 57%; p = 0.003). The favourable tolerability profile of TTS-fentanyl was also reflected in both the patient and the investigator global evaluation of the treatment. Patient assessment favoured TTS-fentanyl treatment in terms of a significantly lower rate of troublesome side-effects ('quite a bit' to 'very much' troublesome side-effects in 14% vs 36% of patients; p = 0.003) and less interruption of daily activities (absence of any interruption of daily activities in 88% vs 63% of patients; p = 0.012). Investigators scored TTS-fentanyl as significantly better with respect to 'side-effects' (p = 0.039) and 'overall impression' (p = 0.013). Sub-analyses of opioid-naïve users gave similar results.\n These data indicate that TTS-fentanyl, when used as an opioid of first choice in the treatment of cancer-related pain, is as effective as, but better tolerated than, SRM, including in opioid-naïve patients.", "Long-term intraspinal infusions of opioid drugs are being increasingly utilized in patients with noncancer pain. Despite this, there is a lack of long-term information, including success and failure rates for pain relief and technical problems. During a 5-year period, 18 noncancer patients underwent implantation of programmable infusion pumps for long-term intrathecal opioid infusion. Patients had (a) neuropathic pain, (b) had failed or been ineligible for noninvasive treatments, and (c) obtained greater than 50% pain relief with intrathecal trial infusions of morphine sulfate or sufentanil citrate. A disinterested third-party reviewer evaluated patients at the most recent follow-up. Sixty-one percent (11/18) of patients had good or fair pain relief with mean follow-up 2.4 +/- 0.3 years (0.8-4.7 years). Average numeric pain scores decreased by 39% +/- 4.3%. Five of the 11 responders required lower opioid doses (12-24 mg/day morphine) and the remaining six patients required higher opioid doses (> 34 mg/day morphine). Failure of long-term pain relief occurred in 39% (7/18) despite good pain relief in trial infusions and the use of both morphine and sufentanil. Technical problems developed in 6/18 patients but appeared to be preventable with further experience. Long-term intrathecal opioid infusions can be effective in treatment of neuropathic pain but might require higher infusion doses.", "To evaluate the efficacy of the combination of epidural ketamine and morphine compared with epidural morphine alone for postoperative pain relief following major upper abdominal surgery.\n Prospective, randomized, double-blinded study.\n Tertiary care referral and teaching hospital.\n 46 ASA physical status I and II patients who underwent major upper abdominal procedures.\n Patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg whereas patients in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine postoperatively.\n A blinded observer using a visual analog scale (VAS) for pain assessment followed up patients for 48 hours postoperatively. Top-up dose of epidural morphine was provided when VAS was higher than 4. Analgesic requirements and side effects were compared between the two groups.\n Only 40 patients completed the study. There were no differences between the two groups with respect to age, gender, weight, duration, or type of surgical procedure or intraoperative opioid requirements. Onset of analgesia was faster (p < 0.001) in Group 2 (11 min) than in Group 1 patients (25 min). The time for first requirement of analgesia was significantly (p < 0.01) longer (19.8 +/- 9.8 hours) in Group 2 patients than Group 1 (12.8 +/- 6.2 hours). Total number of supplemental doses of epidural morphine required in the first 48 hours postoperatively was also significantly less (p < 0.005) in Group 2 compared to Group 1. Patients in Group 2 had higher sedation scores than Group I patients for the first 2 hours postoperatively. None of the patients in either group developed hallucinations or respiratory depression. Other side effects such as pruritus, nausea, and vomiting were also similar in both groups.\n The addition of epidural ketamine 1 mg/kg to morphine 50 microg/kg improved analgesia after major upper abdominal surgery without increasing side effects." ]

[ "7706955", "12221344", "19674713", "11353937", "19770596", "21303529", "12759322", "19066648", "16949939" ]

[ "Phasic exercises for cervical rehabilitation after \"whiplash\" trauma.", "A randomized controlled trial of exercise and manipulative therapy for cervicogenic headache.", "A feasibility study assessing manual therapies to different regions of the spine for patients with subacute or chronic neck pain.", "A pilot randomized clinical trial on the relative effect of instrumental (MFMA) versus manual (HVLA) manipulation in the treatment of cervical spine dysfunction.", "Neck/shoulder exercise for neck pain in air force helicopter pilots: a randomized controlled trial.", "A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain.", "Active neck muscle training in the treatment of chronic neck pain in women: a randomized controlled trial.", "Immediate effects of inhibitive distraction on active range of cervical flexion in patients with neck pain: a pilot study.", "Immediate effects on neck pain and active range of motion after a single cervical high-velocity low-amplitude manipulation in subjects presenting with mechanical neck pain: a randomized controlled trial." ]

[ "To assess whether \"phasic\" exercises, including rapid eye-head-neck-arm movements, can benefit patients with chronic cervical injuries.\n A randomized, controlled, double blind study involving 30 chronic patients, who were allocated to either group 1 or group 2. The study period was for 8 wk.\n The study was conducted in a private practice.\n Thirty chronic motor vehicle accident patients who continued to experience increased pain/soreness/stiffness of the cervical musculature with sports/activities requiring rapid head neck movements were selected for the study.\n Group 1 patients (n = 15) had standard exercises (stretching/isometric/isokinetic) and chiropractic therapy. Group 2 patients (n = 15) had \"phasic\" exercises and chiropractic therapy. Patients in both groups exercised for a minimum of four times weekly, for 8 wk.\n Pre and Post Pain and Disability Index was administered to both groups.\n Group 1, which had standard exercises and chiropractic therapy, improved by 7.4% (p > .05). Group 2, which had \"phasic\" exercises and chiropractic therapy, improved by 48.3% (p > .001). Confounders were identified, which explains the minimal improvement of group 1 and the remarkable results of group 2.\n It would appear that any rehabilitation program for chronic neck-injured patients should involve exercises that address the following: eye-head-neck-arm coordinated movements, coordination of the entire vertebral column,/ and return the \"phasic\" component of the musculature to functional levels. Additional studies will address the effect of these exercises on the strength, range of motion and pain improvement of the cervical spine in normal, acute and chronic patients.", "A multicenter, randomized controlled trial with unblinded treatment and blinded outcome assessment was conducted. The treatment period was 6 weeks with follow-up assessment after treatment, then at 3, 6, and 12 months.\n To determine the effectiveness of manipulative therapy and a low-load exercise program for cervicogenic headache when used alone and in combination, as compared with a control group.\n Headaches arising from cervical musculoskeletal disorders are common. Conservative therapies are recommended as the first treatment of choice. Evidence for the effectiveness of manipulative therapy is inconclusive and available only for the short term. There is no evidence for exercise, and no study has investigated the effect of combined therapies for cervicogenic headache.\n In this study, 200 participants who met the diagnostic criteria for cervicogenic headache were randomized into four groups: manipulative therapy group, exercise therapy group, combined therapy group, and a control group. The primary outcome was a change in headache frequency. Other outcomes included changes in headache intensity and duration, the Northwick Park Neck Pain Index, medication intake, and patient satisfaction. Physical outcomes included pain on neck movement, upper cervical joint tenderness, a craniocervical flexion muscle test, and a photographic measure of posture.\n There were no differences in headache-related and demographic characteristics between the groups at baseline. The loss to follow-up evaluation was 3.5%. At the 12-month follow-up assessment, both manipulative therapy and specific exercise had significantly reduced headache frequency and intensity, and the neck pain and effects were maintained (P < 0.05 for all). The combined therapies was not significantly superior to either therapy alone, but 10% more patients gained relief with the combination. Effect sizes were at least moderate and clinically relevant.\n Manipulative therapy and exercise can reduce the symptoms of cervicogenic headache, and the effects are maintained.", "The purpose of this project was to develop and test protocols for a randomized clinical trial of a combined therapeutic approach (thoracic spine and sacroiliac joint high-velocity, low-amplitude spinal manipulation [HVLA SM] + cervical spine postisometric relaxation) and cervical spine HVLA SM for patients with subacute or chronic neck pain.\n Patients were recruited in the Quad Cities in Iowa and Illinois. After a baseline assessment visit, eligible patients were randomly assigned to cervical spine HVLA SM or to the combined therapeutic approach for 4 treatment visits over 2 weeks. Outcome assessments included the Neck Disability Index, visual analog scale, and posttreatment response questionnaire. Patient outcomes were not aggregated or compared by treatment group.\n It took approximately 8 months of planning, which included the development of forms and protocols, pretesting the forms, and training staff and clinicians in the standardized protocols. Twelve participants were screened, and 6 patients were enrolled and randomly allocated to care over a 6-week period. All patients completed 5 visits. Five of 6 patients had an improvement on the Neck Disability Index. On the visual analog scale, 2 patients improved at 2 weeks, whereas the other 4 got worse. Five patients completed the posttreatment response questionnaire; 2 of the 5 indicated they experienced discomfort or an unpleasant reaction from the study treatments.\n Designing a successful feasibility randomized clinical trial requires considerable planning, development and pretesting of the forms and protocols, and training clinicians and staff for standardized protocols. Patients were willing to be randomized, follow treatment protocols, complete baseline and outcome assessments, and return 83% of the follow-up questionnaires.", "To determine the relative effect of instrument-delivered thrust cervical manipulations in comparison with traditional manual-delivered thrust cervical manipulations in the treatment of cervical spine dysfunction.\n Prospective, randomized, comparative clinical trial.\n Outpatient chiropractic clinic, Technikon Natal, South Africa.\n Thirty patients diagnosed with neck pain and restricted cervical spine range of motion without complicating pathosis for at least 1 month were included in the study.\n The patients were randomized into 2 groups. Those in one group received mechanical force, manually assisted (MFMA) manipulation to the cervical spine, delivered by means of a hand-held instrument (Activator II Adjusting Instrument). Those in the other group received specific contact high-velocity, low-amplitude (HVLA) manipulation consisting of standard Diversified rotary/lateral break techniques to the cervical spine. Each group received only the specific therapeutic intervention, no other treatment modalities or interventions (including medication) being used, until asymptomatic status was achieved or a maximum of 8 treatments had been received. Main Outcome Measures: Both treatment groups were assessed through use of subjective (Numerical Pain Rating Scale 101, McGill Short-Form Pain Questionnaire, and Neck Disability Index) and objective (goniometer cervical range of motion) measurement parameters at specific intervals during the treatment period and at 1-month follow-up. The data were assessed through use of 2-tailed nonparametric paired and unpaired analysis, descriptive statistics, and power analysis of the data.\n The results indicate that both treatment methods had a positive effect on the subjective and objective clinical outcome measures, no significant difference being observed between the 2 groups (P < .025). The subjective data from all 3 questionnaires showed statistically significant changes from initial to final consultations as well as from initial consultation to 1-month follow-up (P < .025). The objective range of motion measures showed statistically significant changes in the MFMA group for left and right rotation and left and right lateral flexion from initial consultation to final consultations and for right rotation and right lateral flexion from initial consultation to 1-month follow-up. The HVLA group showed only the change in left rotation from initial to final consultations and from initial consultation to 1-month follow-up to be statistically significant.\n The results of this clinical trial indicate that both instrumental (MFMA) manipulation and manual (HVLA) manipulation have beneficial effects associated with reducing pain and disability and improving cervical range of motion in this patient population. A randomized, controlled clinical trial in a similar patient base with a larger sample size is necessary to verify the clinical relevance of these findings.", "The study was a randomized, controlled trial with blinded outcome assessment. A 6-week intervention was followed up directly afterwards and after 12 months.\n The purpose was to evaluate the preventive efficacy of a neck/shoulder exercise regimen for neck pain in air force helicopter pilots.\n Neck pain is a significant medical problem in modern military aviation. Research shows neck-muscle dysfunction in subjects with various neck disorders. So far, evidence for neck exercise as prevention or early intervention is sparse, and few trials use randomized controlled design.\n Sixty-eight helicopter pilots on active flying duty with or without neck pain were randomly assigned to a supervised neck/shoulder exercise regimen or a control group receiving no such regimen. The key outcome was change in the prevalence of neck pain cases at the 12-month follow-up, rated for the previous week and the previous 3 months. Secondary outcomes included neck-flexor surface electromyographic activity during active craniocervical flexion and pain-related fear regarding physical activity. In addition, a secondary regression analysis included preintervention predictors that may be associated with change in prevalence of neck-pain cases at the 12-month follow-up.\n Eighty-two percent (56/68) of the participants assigned at random completed the intervention and provided data at month 12. Regression analysis showed a reduction in the prevalence of neck pain cases in the exercise group, which was significant for pain ratings during the previous week, OR = 3.2 (95% CI = 1.3-7.8), and previous 3 months, OR = 1.9 (95% CI = 1.2-3.2). Electromyographic activity at the highest contraction level was significantly reduced in the exercise group, P < 0.05, whereas no between-groups effect emerged for pain-related fear. Results from the secondary analysis showed that general strength training for more than 1 hour per week before the intervention predicted reduction in prevalence of pain at follow-up.\n A supervised neck/shoulder exercise regimen was effective in reducing neck pain cases in air force helicopter pilots. This was supported by improvement in neck-flexor function postintervention in regimen members. However, no effect emerged for pain-related fear. General strength training before the intervention predicted reduction in prevalence of pain at follow-up.", "Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program.\n Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire.\n Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase.\n This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP.\n ClinicalTrials.gov: NCT00566930.", "Active physical training is commonly recommended for patients with chronic neck pain; however, its efficacy has not been demonstrated in randomized studies.\n To evaluate the efficacy of intensive isometric neck strength training and lighter endurance training of neck muscles on pain and disability in women with chronic, nonspecific neck pain.\n Examiner-blinded randomized controlled trial conducted between February 2000 and March 2002.\n Participants were recruited from occupational health care systems in southern and eastern Finland.\n A total of 180 female office workers between the ages of 25 and 53 years with chronic, nonspecific neck pain.\n Patients were randomly assigned to either 2 training groups or to a control group, with 60 patients in each group. The endurance training group performed dynamic neck exercises, which included lifting the head up from the supine and prone positions. The strength training group performed high-intensity isometric neck strengthening and stabilization exercises with an elastic band. Both training groups performed dynamic exercises for the shoulders and upper extremities with dumbbells. All groups were advised to do aerobic and stretching exercises regularly 3 times a week.\n Neck pain and disability were assessed by a visual analog scale, the neck and shoulder pain and disability index, and the Vernon neck disability index. Intermediate outcome measures included mood assessed by a short depression inventory and by maximal isometric neck strength and range of motion measures.\n At the 12-month follow-up visit, both neck pain and disability had decreased in both training groups compared with the control group (P<.001). Maximal isometric neck strength had improved flexion by 110%, rotation by 76%, and extension by 69% in the strength training group. The respective improvements in the endurance training group were 28%, 29%, and 16% and in the control group were 10%, 10%, and 7%. Range of motion had also improved statistically significantly in both training groups compared with the control group in rotation, but only the strength training group had statistically significant improvements in lateral flexion and in flexion and extension.\n Both strength and endurance training for 12 months were effective methods for decreasing pain and disability in women with chronic, nonspecific neck pain. Stretching and fitness training are commonly advised for patients with chronic neck pain, but stretching and aerobic exercising alone proved to be a much less effective form of training than strength training.", "The purpose of this pilot study was to examine the immediate effects of a manual therapy technique called Inhibitive Distraction (ID) on active range of motion (AROM) for cervical flexion in patients with neck pain with or without concomitant headache. A secondary objective of this study was to see whether patient subgroups could be identified who might benefit more from ID by studying variables such as age, pain intensity, presence of headache, or pre-intervention AROM. We also looked at patients' ability to identify pre- to post-intervention changes in their ability to actively move through a range of motion. Forty subjects (mean age 34.7 years; range 16-48 years) referred to a physical therapy clinic due to discomfort in the neck region were randomly assigned to an experimental and a control group. We used the CROM goniometer to measure pre- and post-intervention cervical flexion AROM in the sagittal plane within a single treatment session. The between-group difference in AROM increase was not statistically significant at P<0.05 with a mean post-intervention increase in ROM of 2.4 degrees (SD 6.2 degrees ) for the experimental group and 1.2 degrees (SD 5.8 degrees ) for the placebo group. We were also unable to identify potential subgroups more likely to respond to ID, although a trend emerged for greater improvement in chronic patients with headaches, lower pain levels, and less pre-intervention AROM. In the experimental group and in both groups combined, subjects noting increased AROM indeed had a significantly greater increase in AROM than those subjects not noting improvement. In conclusion, this study did not confirm immediate effects of ID on cervical flexion AROM but did provide indications for potential subgroups likely to benefit from this technique. Recommendations are provided with regard to future research and clinical use of the technique studied.", "The objective of this study is to analyze the immediate effects on neck pain and active cervical range of motion after a single cervical high-velocity low-amplitude (HVLA) manipulation or a control mobilization procedure in mechanical neck pain subjects. In addition, we assessed the possible correlation between neck pain and neck mobility.\n Seventy patients with mechanical neck pain (25 males and 45 females, aged 20-55 years) participated in this study. The lateral gliding test was used to establish the presence of an intervertebral joint dysfunction at the C3 through C4 or C4 through C5 levels. Subjects were divided randomly into either an experimental group, which received an HVLA thrust, or a control group, which received a manual mobilization procedure. The outcome measures were active cervical range of motion and neck pain at rest assessed pretreatment and 5 minutes posttreatment by an assessor blinded to the treatment allocation of the patient. Intragroup and intergroup comparisons were made with parametric tests. Within-group effect sizes were calculated using Cohen's d coefficient.\n Within-group changes showed a significant improvement in neck pain at rest and mobility after application of the manipulation (P < .001). The control group also showed a significant improvement in neck pain at rest (P < .01), flexion (P < .01), extension (P < .05), and both lateral flexions (P < .01), but not in rotation. Pre-post effect sizes were large for all the outcomes in the experimental group (d > 1), but were small to medium in the control mobilization group (0.2 < d < 0.6). The intergroup comparison showed that the experimental group obtained a greater improvement than the control group in all the outcome measures (P < .001). Decreased neck pain and increased range of motion were negatively associated for all cervical motions: the greater the increase in neck mobility, the less the pain at rest.\n Our results suggest that a single cervical HVLA manipulation was more effective in reducing neck pain at rest and in increasing active cervical range of motion than a control mobilization procedure in subjects suffering from mechanical neck pain." ]

[ "8780077", "7823066", "10486394", "8601999", "3919805", "19169651", "1814875", "2711309", "10441604" ]

[ "A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors.", "Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial.", "Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects.", "Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy.", "Which drug for the adult epileptic patient: phenytoin or valproate?", "Safety and feasibility of switching from phenytoin to levetiracetam monotherapy for glioma-related seizure control following craniotomy: a randomized phase II pilot study.", "Comparison of sodium valproate and phenytoin as single drug treatment in generalised and partial epilepsy.", "Prophylactic anticonvulsants for prevention of immediate and early postcraniotomy seizures.", "Phenobarbital compared with phenytoin for the treatment of neonatal seizures." ]

[ "Seizures occur after the diagnosis of brain tumors in up to 40% of patients. Prophylactic anticonvulsants are widely advocated despite a lack of convincing evidence of their efficacy in preventing first seizures. We conducted a randomized, double-blind, placebo-controlled study comparing the incidence of first seizures in divalproex sodium- and placebo-treated patients with newly diagnosed brain tumors.\n Patients who had not previously had a seizure were randomized within 14 days of diagnosis of their brain tumor to receive either divalproex sodium or placebo. All patients had at least one supratentorial brain lesion, a Karnofsky Performance Score (KPS) > or = 50%, and no previous anticonvulsant use or other brain disease. Compliance and adequacy of dosing were assessed by pill counts and monthly blood levels.\n Seventy-four of 75 consecutive eligible patients were entered in this study. Median follow-up was 7 months. The drug and placebo groups did not differ significantly in age, sex, KPS, primary tumor type, number or location of brain lesions, frequency of brain surgery, or pretreatment EEG. Thirteen of 37 patients (35%) receiving divalproex sodium and 9 of 37 patients (24%) on placebo had seizures. The odds ratio for a seizure in the divalproex sodium arm relative to the placebo arm was 1.7 (95% CI 0.6 to 4.6; p = 0.3). The hypothesis that anticonvulsant prophylaxis provides a reduction in the frequency of first seizure as small as 30% was rejected (p = 0.05).\n Anticonvulsant prophylaxis with divalproex sodium is not indicated for patients with brain tumors who have not had seizures.", "Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.", "To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy.\n A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased.\n Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences.\n For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy.", "The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy.\n Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission.\n The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.", "A series of 140 previously untreated patients with tonic-clonic or partial seizures were randomised to receive either phenytoin or sodium valproate. There was no difference between the treatment groups in pretreatment variables that might influence outcome. Sodium valproate and phenytoin in the treatment of tonic-clonic or partial seizures showed no difference in efficacy as regards time to two year remission or time to first seizure. When the possible prognostic factors were studied, including history and results of clinical examination and investigations before treatment; the only factor which influenced the proportion of patients achieving two year remission was type of seizure. Patients with a clinical history of partial seizures did significantly less well than those with a history of tonic-clonic seizures only. This study showed no major difference in efficacy between sodium valproate and phenytoin in adults with recent onset of epilepsy, irrespective of the type of seizures that the patient suffered.", "Seizures are common in patients with gliomas, and phenytoin (PHT) is frequently used to control tumor-related seizures. PHT, however, has many undesirable side effects (SEs) and drug interactions with glioma chemotherapy. Levetiracetam (LEV) is a newer antiepileptic drug (AED) with fewer SEs and essentially no drug interactions. We performed a pilot study testing the safety and feasibility of switching patients from PHT to LEV monotherapy for postoperative control of glioma-related seizures. Over a 13-month period, 29 patients were randomized in a 2:1 ratio to initiate LEV therapy within 24 h of surgery or to continue PHT therapy. 6 month follow-up data were available for 15 patients taking LEV and for 8 patients taking PHT. In the LEV group, 13 patients (87%) were seizure-free. In the PHT group, 6 patients (75%) were seizure-free. Reported SEs at 6 months was as follows (%LEV/%PHT group): dizziness (0/14), difficulty with coordination (0/29), depression (7/14) lack of energy or strength (20/43), insomnia (40/43), mood instability (7/0). The pilot data presented here suggest that it is safe to switch patients from PHT to LEV monotherapy following craniotomy for supratentorial glioma. A large-scale, double-blinded, randomized control trial of LEV versus PHT is required to determine seizure control equivalence and better assess differences in SEs.", "Ninety four patients of generalised and partial epilepsy were randomly assigned to treatment with sodium valproate (49 cases) or phenytoin (45 cases). Serum levels were monitored. Cases were evaluated after 4, 12, 24 weeks of treatment. Both drugs were found to be equally effective in controlling generalised seizures. However, valproate is better in partial seizures. No correlation could be established. Side effects were minor with both the drugs.", "Phenytoin (15 mg/kg) was administered intravenously to 189 patients shortly before their intracranial, supratentorial surgery was completed. Intravenous phenytoin of 5-6 mg/kg/day in three divided doses was administered daily for the first 3 postoperative days. Therapeutic serum levels (10-20 micrograms/mL) were achieved in 113 (59.8%) patients. An equally constituted, randomized control group of 185 patients received a placebo under identical conditions. The group receiving phenytoin had only one immediate and two early postoperative seizures. The 185 controls had four immediate and nine early postoperative seizures. None of the follow-up computed tomography scans of the patients with seizures showed postoperative hematoma. One patient had a significant tension pneumocranium, a possible cause of postoperative seizures. To avoid a decrease in the serum anticonvulsant level due to intraoperative blood loss, it is suggested that for patients who need an urgent or emergent craniotomy, prophylatic anticonvulsant medication should be given at least 20 minutes before completion of wound closure.", "Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly.\n From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 microg per milliliter for phenobarbital and 3 microg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria.\n Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment.\n Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates." ]

[ "8813270", "3511382", "6150321", "1658648", "20698956", "9066350", "2893583", "7998769", "16877299" ]

[ "Plasma-exchange therapy in chronic inflammatory demyelinating polyneuropathy. A double-blind, sham-controlled, cross-over study.", "Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy.", "Beneficial effects of plasma exchange in acute inflammatory polyradiculoneuropathy.", "Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance.", "Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial.", "Appropriate number of plasma exchanges in Guillain-Barré syndrome. The French Cooperative Group on Plasma Exchange in Guillain-Barré Syndrome.", "Efficiency of plasma exchange in Guillain-Barré syndrome: role of replacement fluids. French Cooperative Group on Plasma Exchange in Guillain-Barré syndrome.", "A plasma exchange versus immune globulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy.", "Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment." ]

[ "Eighteen patients with definite, untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) of chronic progressive (nine patients) or relapsing course (nine patients) were randomized prospectively to receive 10 plasma-exchange (PE) or sham plasma-exchange (SPE) treatments over 4 weeks in a double-blind trial. After a wash-out period of 5 weeks or when they returned to baseline scores, patients were crossed over to the alternate treatments. Neurological function was assessed serially using a quantitative neurological disability score (NDS), a functional clinical grade (CG) and grip strength (GS) measurements. Electrophysiological studies were done at the beginning and end of each treatment. A primary 'intention to treat' analysis showed significant improvement with PE in all clinical outcome measures: NDS by 38 points, P < 0.001; CG by 1.6 points, P < 0.001; GS by +13 kg, P < 0.003 and in selected electrophysiological measurements, sigma proximal CMAP, P < 0.01; sigma motor conduction velocities, P < 0.006; sigma distal motor latencies, P < 0.01. Fifteen patients completed the trial and of those, 12 patients (80%) improved substantially with PE; i.e. five out of seven patients with chronic progressive course and seven out of eight patients with relapsing CIDP improved. There were three drop-outs; one patient lost venous access; one patient suffered a stroke and one patient left the trial to receive open treatment elsewhere. The improvement in motor functions correlated with the electrophysiological data, i.e. with improved motor conduction velocities and reversal of conduction block. Eight of 12 PE responders (66%) relapsed within 7-14 days after stopping PE. All improved with subsequent open label PE; all but two patients required long-term immunosuppressive drug therapy for stabilization. The PE non-responders improved with prednisone. We conclude that PE is a very effective adjuvant therapy for CIDP of both chronic progressive and relapsing course; concurrent immunosuppressive drug treatment is required. Exchange treatments should be given two to three times per week until improvement is established; the treatment frequency should then be tapered over several months.", "Plasma exchange has been reported to be efficacious in chronic inflammatory demyelinating polyradiculoneuropathy. We performed a prospective double-blind trial in which patients with static or worsening disease were randomly assigned to plasma exchange (n = 15) or to sham exchange (n = 14) for three weeks. After three weeks, we observed statistically significant differences in combined measurements of nerve conduction (total, motor, proximal, velocity, and amplitude) favoring patients who had received plasma exchange. Improvement to a greater degree than for any patient receiving sham exchange was detected in the neurologic-disability score in five patients (P = 0.025) and in subset scores for weakness and reflex in four patients (P less than 0.057). We conclude that for some patients with chronic inflammatory demyelinating polyradiculoneuropathy, plasma exchange has an ameliorating effect on neurologic dysfunction and nerve conduction, but in others no improvement is observed. Because plasma was replaced with normal serum albumin, a humoral factor or factors may have a role in the neurologic deficit of this disorder.", "The results of a controlled trial in which 38 patients with severe acute inflammatory polyradiculoneuropathy took part indicate that plasma exchange favourably influenced the course of the disease. Significant benefits were seen in time until onset of improvement, course of muscular weakness, improvement in disability grades over the first 2 months, and working capacity after 1 month. Cost-benefit analysis showed that the exchange treatment resulted in net financial savings. The results suggest that plasma exchange may have a role in the treatment of severe acute inflammatory polyradiculoneuropathy.", "Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) has been treated with plasma exchange, intravenous immune globulin, and chemotherapy, but the effectiveness of these treatments remains uncertain.\n We randomly assigned 39 patients with stable or worsening neuropathy and MGUS of the IgG, IgA, or IgM type to receive either plasma exchange twice weekly for three weeks or sham plasma exchange, in a double-blind trial. The patients who initially underwent sham plasma exchange subsequently underwent plasma exchange in an open trial.\n In the double-blind trial, the average neuropathy disability score improved by 2 points from base line (from 62.5 to 60.5) in the sham-exchange group and by 12 points (from 58.3 to 46.3) in the plasma-exchange group (P = 0.06). A similar difference was observed in the weakness score, a component of the neuropathy disability score (improvement, 1 and 10 points, respectively; P = 0.07). After treatment the summed compound muscle action potentials of motor nerves were 1.2 mV lower (worse) than at base line in the sham-exchange group and 0.4 mV higher (better) in the plasma-exchange group (P = 0.07). The greater degree of improvement with plasma exchange was equal in magnitude to or greater than the difference between not being able to walk on the heels or toes and being able to perform these activities. Changes in the vibratory detection threshold, summed motor-nerve conduction velocity, and sensory-nerve action potentials did not differ significantly between the treatment groups. In the open trial, in which patients who initially underwent sham exchange were treated with plasma exchange, the neuropathy disability score (P = 0.04), weakness score (P = 0.07), and summed compound muscle action potentials (P = 0.07) improved more with plasma exchange than they had with sham exchange. In both the double-blind and the open trial, those with IgG or IgA gammopathy had a better response to plasma exchange than those with IgM gammopathy.\n Plasma exchange appears to be efficacious in neuropathy associated with MGUS, especially of the IgG or IgA type.", "Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and/or low dose inotropic therapy. The mechanisms underlying this benefit remain uncertain. The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery.\n Randomised, controlled, single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery. For eight hours after surgery, intra-venous fluid therapy was guided by measurements of central venous pressure (CVP group), or stroke volume (SV group). In a third group stroke volume guided fluid therapy was combined with dopexamine (0.5 mcg/kg/min) (SV & DPX group).\n 135 patients were recruited (n = 45 per group). In the SV & DPX group, increased global oxygen delivery was associated with improved sublingual (P < 0.05) and cutaneous microvascular flow (P < 0.005) (sublingual microscopy and laser Doppler flowmetry). Microvascular flow remained constant in the SV group but deteriorated in the CVP group (P < 0.05). Cutaneous tissue oxygen partial pressure (PtO2) (Clark electrode) improved only in the SV & DPX group (P < 0.001). There were no differences in serum inflammatory markers. There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group (CVP group ten patients (22%); pooled SV and SV & DPX groups seven patients (8%); P = 0.03) (post hoc analysis).\n Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery, microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery. These observations may explain improved clinical outcomes associated with this treatment in previous trials.\n ISRCTN 94850719.", "Plasma exchange (PE) is the standard treatment in Guillain-Barré syndrome (GBS) patients who have lost the ability to walk. The effect of exchanges before this stage and the optimal number of exchanges for the other patients are still unknown. We randomized 556 GBS patients according to severity and number of exchanges as follows: Zero versus 2 PEs for patients who could walk-with or without aid-but not run, or who could stand up unaided (mild group); 2 versus 4 PEs for patients who could not stand up unaided (moderate group); and 4 versus 6 PEs for mechanically ventilated patients (severe group). In the mild group, 2 PEs were more effective than none for time to onset of motor recovery (median, 4 vs 8 days, respectively). In the moderate group, 4 PEs were more beneficial than 2 for time to walk with assistance (median, 20 vs 24 days) and for 1-year full muscle-strength recovery rate (64% vs 46%). Six PEs were no more beneficial than 4 in the severe cases. Patients with mild GBS on admission should receive 2 PEs. Patients with moderate and severe forms should benefit from 2 further exchanges.", "The goals of this multicenter controlled trial were: (1) to study the short-term effect of plasma exchange in the Guillain-Barré syndrome when applied alone within 17 days of onset of the disease; and (2) to compare two replacement fluids, diluted albumin and fresh frozen plasma (FFP) with regard to efficacy and morbidity. Two hundred twenty patients were included, 111 in the control group, 109 in the plasma exchange group, 57 of whom were assigned to receive albumin and 52 to receive fresh frozen plasma. Treatment consisted of four plasma exchanges of two plasma volumes each, initiated on the day of randomization and repeated on alternate days. Significant short-term benefits appeared in the group that received plasma exchange as demonstrated by the reduction in the proportion of patients who required assisted ventilation after randomization, and the decrease in time before beginning weaning from ventilator, time to onset of motor recovery, and time to walk with and without assistance. No statistically significant difference was found between the group that received albumin and the group that received fresh frozen plasma. Incidents during exchanges and complications related to the plasma exchange were more frequent in patients who received fresh frozen plasma. Plasma exchange is beneficial in Guillain-Barré syndrome when it is carried out early in the course of the disease. Given its risks and the lack of its clear superiority over albumin, however, we recommend that fresh frozen plasma be abandoned in the treatment of Guillain-Barré syndrome.", "Chronic inflammatory demyelinating polyradiculoneuropathy is a paralytic syndrome, causing considerable disability and even death. In controlled clinical trials, plasma exchange prevented or ameliorated neurological deficits, but the efficacy of immune globulin infusion remains unproved. Also unknown is whether immune globulin infusion is as effective, or more effective, than plasma exchange and what dosages and frequencies are best. In this observer-blinded study, using some objective end points not subject to bias (e.g., summated compound muscle action potential), 20 patients with progressive or static polyneuropathy were randomly assigned to receive either of the two treatments for 6 weeks, followed by a washout period, and then were assigned to receive the other treatment. Plasma exchange (twice a week for 3 weeks then once a week for 3 weeks) and immune globulin infusion (0.4 gm/kg once a week for 3 weeks, then 0.2 gm/kg once a week for the next 3 weeks) were used. End points assessed before and after treatment schedules were neurological disability score; muscle weakness of the neurological disability score; summated compound muscle action potentials of ulnar, median, and peroneal nerves; summated sensory nerve action potentials of ulnar and sural nerves; and vibratory detection threshold of the great toe using CASE IV. Observers were masked as to treatment used. Of 20 patients, 13 received both treatments whereas 4 did not worsen sufficiently to receive the second treatment--1 patient left the study during and 2 after the first treatment to receive unscheduled treatment elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)", "D-Ala1-peptide T-amide (DAPTA) has shown neuroprotection in vitro against gp120-induced loss of dendritic arborization and is promulgated as a CCR5 antagonist. A multisite, randomized, double-blind clinical trial of DAPTA versus placebo prior to combination antiretroviral therapy conducted with human immunodeficiency virus (HIV)-1 seropositive participants having cognitive impairment showed no overall cognitive effect, though subgroups with greater impairment and CD4 cell counts of 201 to 500 cells/mm3 at baseline showed significant improvement. The objective of this study was to examine whether intranasal administration of DAPTA at a dose of 2 mg three times per day (tid) was associated with a reduction of cerebrospinal fluid (CSF) and peripheral (plasma and serum) viral load among a subgroup of participants completing 6 months of treatment. Baseline and 6-month CSF (n = 92) and peripheral (plasma n = 33; serum n = 24) viral load were measured by the Roche Ultrasensitive assay, version 1.5, with reflexive use of the AMPLICOR assay and preservation of the blind. A DAPTA treatment indicator variable was tested using generalized linear models on change in viral load. Peripheral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group. No group differences in CSF viral load were found. This retrospective study on a limited subgroup of the original trial sample indicated that DAPTA treatment may reduce peripheral viral load without concomitant CSF effects. Future studies should be undertaken to confirm the existence of this result and the CSF-periphery dissociation observed with respect to HIV-1-associated cognitive-motor impairment." ]

[ "18161613", "17416878", "12384193", "12677565", "16507741", "9734406", "11177061", "9113011", "10195971" ]

[ "Quality of reporting of key methodological items of randomized controlled trials in clinical ophthalmic journals.", "Studying injury prevention: practices, problems, and pitfalls in implementation.", "In the dark: the reporting of blinding status in randomized controlled trials.", "Randomized controlled trials in pediatric surgery: could we do better?", "Efficacy of the North American guidelines for children's agricultural tasks in reducing childhood agricultural injuries.", "Computer-based training for the treatment of partial blindness.", "Randomized trial of enhanced anticipatory guidance for injury prevention.", "Randomised controlled trial of anterior-chamber intraocular lenses.", "Preventing injuries in children: cluster randomised controlled trial in primary care." ]

[ "To evaluate the reporting quality of key methodological items in randomized controlled trials (RCTs) in four general clinical ophthalmology journals.\n The reporting of 11 key methodological items in RCTs published in American Journal of Ophthalmology, Archives of Ophthalmology, British Journal of Ophthalmology and Ophthalmology in the year 2005 was assessed.\n Sixty-seven eligible RCTs were assessed and the mean number of items reported was 6.3 per RCT. No significant difference in the mean number of items reported was found between the four journals (P=0.20). The most frequently reported item was ethics approval and informed consent (97.0%), followed by masking status (85.1%), description of withdrawals (76.1%), adverse events (73.1%), and intention-to-treat analysis (71.6%). Details on sequence generation, randomization restriction, allocation concealment, allocation implementation, patient flow diagrams, and sample size calculation were reported in <50% of the RCTs assessed. Both sample size and page length of the RCTs correlated with the number of methodological items reported (P=0.024 and P=0.008, respectively).\n Similar to other specialties, rooms for improvement exist in the reporting of key methodological items of RCTs in clinical ophthalmic journals. Stricter adoption of the CONSORT statement might enhance the reporting quality of RCTs in ophthalmic journals.", "This prospective, randomized, controlled trial was conducted to determine feasibility and effectiveness of a chronic care model approach to injury prevention compared with standard anticipatory guidance. Enrolled caregivers of children aged 0 to 5 years received focused counseling from a physician and health assistant, educational handouts, phone follow-up, and access to free safety devices and automobile restraint evaluations. Only 35.1% of eligible parents participated. Home visits were completed at 6 months to observe safety practices. Injuries were gleaned from parent report and medical record review. Safety practices were evaluated in 27 households. Chart review showed no significant difference in the number of medically attended injuries between groups (P = 0.6). The impact of the chronic care model on injury prevention in primary care could not be determined with certainty. Evaluating effectiveness of injury prevention strategies on actual safety practices with direct observation is challenging.", "To determine the quality of reporting of blinding in randomized controlled trials (RCTs), we evaluated 40 consecutive RCTs published in each of five leading journals. We noted whether authors reported the blinding status of participants, health care providers, data collectors, judicial assessors of outcomes, data analysts, and manuscript writers. Explicit reporting of blinding status occurred in <25% of RCTs for all groups. Eighty-three RCTs, reported as double-blind, provided eight combinations of blinded groups. In conclusion, prestigious journals do not currently report blinding status optimally. To do so, journals should abandon the term \"double blind\" and explicitly report the blinding status of the groups involved in RCTs. Until such reporting occurs, clinicians will be left with uncertainty about the validity of RCTs that guide their clinical practice.", "Randomized controlled trials (RCTs) are accepted as the gold standard for assessing the effectiveness of clinical interventions but are rarely reported in pediatric surgery. Have RCTs submitted to the British Association of Paediatric Surgeons (BAPS) Annual Congress during the last 5 years been adequately designed and large enough to produce a valid result?\n Abstracts accepted by the Annual BAPS Congress meetings between 1996 and 2000 were examined in collaboration with a senior health services researcher. The quality of the design, methodology, statistical analysis and conclusions, and the adequacy of the sample size were assessed for all identifiable clinical RCTs.\n From 760 accepted abstracts, there were only 9 RCTs (1%) of clinical interventions. In only 4 trials was the relevant primary end-point specified at the outset of the study, and none documented the method of randomization. Only one abstract mentioned blinding with respect to the intervention or outcome measure. Sample sizes were inadequate to detect even large clinical differences. To date, only one of these RCTs has been published in an English-language, peer-reviewed journal.\n Clear guidelines exist for the conduct of RCTs, yet compliance with these standards was rarely documented in abstracts of pediatric surgical RCTs presented at BAPS. Sample sizes were inadequate. RCTs in pediatric surgery are difficult to perform, but the specialty would benefit from well-designed, carefully conducted, multicentre, clinical RCTs to advance evidence-based practice.\n Copyright 2003, Elsevier Science (USA). All rights reserved.", "We assessed whether active dissemination of the North American Guidelines for Children's Agricultural Tasks (NAGCAT) reduced childhood agricultural injuries.\n In this randomized controlled trial, lay educators visited intervention farms to review NAGCAT. New York State farms with resident or working children were randomized. Control farms were visited only to collect baseline data. Data on childhood injuries, tasks, and hours worked were obtained quarterly for 21 months. Injury rates per farm were compared between the treatment and control groups, along with time span to occurrence of an injury and to violation of NAGCAT age guidelines.\n Intervention farms were less likely than control farms to violate NAGCAT age guidelines in the areas of all-terrain-vehicle use and tractor and haying operations. Cox proportional hazards regression models showed a significant protective effect of the intervention on preventable injuries after adjustment for important covariates.\n Our results showed that dissemination of NAGCAT reduced rates of work-related childhood agricultural injuries. A comprehensive public health approach is needed to reduce non-work-related childhood injuries.", "Partial blindness after brain injury has been considered non-treatable. To evaluate whether patients with visual-field defects can profit from computer-based visual restitution training (VRT), two independent clinical trials were conducted using patients with optic nerve (n = 19) or post-chiasmatic brain injury (n = 19). In post-chiasma patients, VRT led to a significant improvement (29.4%) over baseline in the ability to detect visual stimuli; in optic nerve patients, the effects were even more pronounced (73.6% improvement). Visual-field enlargements were confirmed by the observation of a visual-field expansion of 4.9 degrees-5.8 degrees of visual angle and improved acuity in optic nerve patients. Ninety five percent of the VRT-treated patients showed improvements, 72.2% confirmed visual improvements subjectively. Patients receiving a placebo training did not show comparable improvements. In conclusion, VRT with a computer program improves vision in patients with visual-field defects and offers a new, cost-effective therapy for partial blindness.", "To develop and evaluate an injury prevention anticipatory guidance training program for pediatric residents.\n Thirty-one residents were randomly assigned to an intervention or control group. Both groups attended a 1-hour seminar about injury prevention and the American Academy of Pediatrics TIPP (The Injury Prevention Program) materials. The intervention group also received 5 hours of experiential instruction on injury prevention content and counseling skills (SAFE Counseling Framework). Families with infants from birth to age 6 months were enrolled in the study (N = 196); they were followed up until the child was aged 12 to 18 months. Data were collected by means of baseline and follow-up interviews, audiotapes of medical visits, parent exit surveys, and home observations.\n A hospital-based continuity clinic that serves families living in low-income, inner-city neighborhoods.\n Physician counseling and parent satisfaction, knowledge, beliefs, and behaviors.\n Parents seen by physicians in the intervention group received significantly more injury prevention counseling for 5 of the 6 safety practices, and they were significantly more satisfied with the help their physicians provided on safety topics. They were no less satisfied with their physicians' counseling on other anticipatory guidance topics. Parents' knowledge, beliefs, and home safety behaviors did not differ between the 2 groups.\n The frequency and impact of pediatric counseling can be enhanced by experiential training that targets specific injury hazards. Because low-income families face many barriers to carrying out the recommended safety practices, supplemental strategies are needed to ensure safer homes.", "There are an estimated 16 million people blind in both eyes with cataracts. Most live in rural areas of developing countries where surgical resources are scarce. There is no consensus on the most appropriate type of intraocular lens in situations where high-volume low-cost surgery is required. This study was undertaken to evaluate the safety of multiflex open-loop anterior-chamber lenses (ACIOLs).\n 2000 people attending Lahan Eye Hospital, southern Nepal, with bilateral cataracts reducing vision to 6/36 or less were randomly allocated to receive standard surgery--intracapsular extraction (ICCE) with aphakic correction--or ICCE with an ACIOL in their first operated eye. The primary outcome was a visual acuity of less than 6/60 in the operated eye at 1 year follow-up. Visual acuity was measured for 91% of the cohort at 1 year. The sample size was estimated to detect a doubling in poor visual outcome from an estimated rate of 4% in the standard surgery (control) group.\n The median (range) time taken to do the surgery was 6.0 (3.0-17.2) min for the ACIOL group and 4.1 (2.4-10.3) min for the control group. 1 year after surgery, 5.0% of the ACIOL group and 5.4% of controls had functional vision less than 6/60 (OR 0.93 [0.60-1.43], p = 0.71). The causes of poor vision in the ACIOL and control groups were: correctable refractive error (22 and 29), uveitis/secondary glaucoma (13 and two), endophthalmitis (four and seven), pre-existing eye disease (four and five), retinal detachment (none and four), cystoid macular oedema (two and none), corneal ulcer (one and one), and corneal decompensation (none and one).\n This study provides evidence that, in rural areas of developing countries, multiflex open-loop ACIOLs can be implanted safely by experienced ophthalmologists after routine ICCE, avoiding the disadvantages of aphakic spectacle correction. Further follow-up is planned.", "To assess the effectiveness of safety advice at child health surveillance consultations, provision of low cost safety equipment to families receiving means tested state benefits, home safety checks, and first aid training on frequency and severity of unintentional injuries in children at home.\n Cluster randomised controlled trial.\n 36 general practices in Nottingham.\n All children aged 3-12 months registered with participating practices.\n A package of safety advice at child health surveillance consultations at 6-9, 12-15, and 18-24 months; provision of low cost safety equipment to families on means tested state benefits; and home safety checks and first aid training by health visitors.\n Primary outcomes measures were frequency and severity of medically attended injuries. Secondary outcome measures were self reported safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk of injury and risk of hazards assessed by postal questionnaire at baseline and follow up at 25 months.\n At baseline, both groups had similar risk factors for injury, sociodemographic characteristics, safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk. No significant difference was found in frequency of at least one medically attended injury (odds ratio 0.97, 95% confidence interval 0.72 to 1.30), at least one attendance at an accident and emergency department for injury (1.02, 0.76 to 1.37), at least one primary care attendance for injury (0.75, 0.48 to 1.17), or at least one hospital admission for injury (0.69, 0.42 to 1.12). No significant difference in the secondary outcome measures was found between the intervention and control groups.\n The intervention package was not effective in reducing the frequency of minor unintentional injuries in children at home, and larger trials are required to assess the effect on more severe injuries." ]

[ "7931476", "12881382", "3666158", "12488405", "12196367", "12001120", "17513815", "6512582", "20619634" ]

[ "First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. Swiss Group for Clinical Cancer Research.", "Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence: definitive results of a phase III randomized trial (SAKK 23/82) comparing tamoxifen with observation.", "A trial of human alpha interferon as an adjuvant agent in breast cancer after loco-regional recurrence.", "Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5.", "Informing breast cancer patients about clinical trials: a randomized clinical trial of an educational booklet.", "A prospective, randomized trial comparing neoadjuvant chemotherapy with radiotherapy alone in patients with advanced nasopharyngeal carcinoma.", "Impact of a peer-delivered telephone intervention for women experiencing a breast cancer recurrence.", "Randomized study of systemic chemotherapy following complete excision of nonosseous sarcomas.", "Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies." ]

[ "We performed a randomized phase III multicenter study to compare systemic treatment versus no treatment after complete excision and radiotherapy for isolated first locoregional recurrence in patients with breast cancer.\n One hundred sixty-seven good-risk patients with an estrogen receptor (ER+) positive recurrence or, in case of unknown receptor status, a disease-free interval (DFI) of greater than 12 months and < or = three recurrent tumor nodules each < or = 3 cm in diameter were entered onto the study. They were randomized to observation subsequent to local treatment or to receive tamoxifen (TAM) until disease progression. Seventy-nine percent of the patients were postmenopausal.\n The median observation period for the entire study population was 6.3 years. The median disease-free survival (DFS) duration was 26 months for observation and 82 months for TAM patients (P = .007). This was mainly due to the reduction of further local recurrences, whereas the occurrence of early distant metastases was delayed. A multivariate analysis identified DFI and treatment with TAM as significant prognostic factors for DFS. The 5-year overall survival (OS) rates were 76% and 74%, respectively (P = .77). DFI was also a prognostic factor for OS.\n Systemic therapy with TAM after isolated locoregional recurrence of breast cancer significantly increased 5-year DFS rates from 36% to 59% compared with observation alone and prolonged median DFS by more than 4.5 years in patients with ER+ tumors or in the case of unknown ER status with a DFI of greater than 12 months and minimal tumor burden. Treatment with TAM currently has no significant impact on OS, but the median survival duration of the study population has not yet been reached.", "Adjuvant systemic treatment for patients with isolated locoregional recurrence (ILRR) of breast cancer is based on a single reported randomized trial. The trial, conducted by the Swiss Group for Clinical Cancer Research, compared tamoxifen (TAM) with observation after complete excision of the ILRR and proper radiotherapy. We performed a definitive analysis of treatment outcome at >11 years of follow-up, after the majority of the patients had a subsequent event of interest. Patient and methods One hundred and sixty-seven patients with 'good-risk' characteristics of disease were randomized. 'Good-risk' was defined as estrogen receptor expression in the ILRR, or having a disease-free interval of >12 months and a recurrence consisting of three or less tumor nodules, each </=3 cm in diameter. Seventy-nine percent of the patients were postmenopausal at randomization.\n The median follow-up time of the surviving patients was 11.6 years. The median post ILRR disease-free survival (DFS) was 6.5 years with TAM and 2.7 years with observation (P = 0.053). The difference was mainly due to reduction of further local relapses (P = 0.011). In postmenopausal patients, TAM led to an increase of DFS from 33% to 61% (P = 0.006). In premenopausal women, 5-year DFS was 60%, independent of TAM medication. For the whole study population, the median post-recurrence overall survival (OS) was 11.2 and 11.5 years in the observation and the TAM group, respectively; premenopausal patients experienced a 5-year OS of 90% for observation compared with 67% for TAM (P = 0.175), while the respective figures for postmenopausal patients were both 75%.\n These definitive results confirmed that TAM significantly improves the post-recurrence DFS of patients after local treatment for ILRR. This beneficial effect does not translate into a detectable OS advantage.", "Thirty-two women who had developed loco-regional recurrence of breast carcinoma were entered into a controlled trial of adjuvant alpha-interferon. All patients had histological confirmation of recurrence, local treatment with radiotherapy and negative staging investigations. They were then randomized to either observation alone, or treatment with human alpha interferon 3 x 10(6) units subcutaneously daily for 1 year. There were no differences detected in the rate of local or distant relapse. With this lack of clinically significant efficacy and a high incidence of side effects, it is concluded that alpha interferon is of doubtful value in the adjuvant treatment of breast cancer.", "Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy.\n Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death.\n With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195).\n Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.", "To evaluate the impact of an educational booklet on women's knowledge of and willingness to participate in a randomized clinical trial of treatment for breast cancer.\n Women undergoing surgery for newly diagnosed early stage breast cancer were randomized to receive, or not, an information booklet explaining the need for and manner in which randomized trials are conducted.\n Eighty-three women with newly diagnosed early stage breast cancer completed a questionnaire assessing attitudes to random clinical trials (RCTs) and were randomized to receive usual information treatment options provided from their oncologist, or the educational booklet in addition to usual information from their oncologist (42 usual information, 41 booklet). Fewer women who received the clinical trials booklet (40% versus 47%) would consider participating in the hypothetical clinical trial (P = 0.6). Mean knowledge scores increased for both groups; moreover, women who did not receive the booklet showed similar improvements to women who received the booklet [mean difference 0.09, 95% confidence interval (CI) -0.66 to 0.83]. In a multivariate analysis women who would consider participating in the clinical trial were more anxious [odds ratio (OR) 5.9, P = 0.02] had involved lymph nodes (OR 5.8, P = 0.02) and were less influenced by negative aspects of clinical trials (OR 7.7, P = 0.0001). After adjustment for these variables women who received the educational booklet were significantly less likely to consider trial participation (OR 0.22, P = 0.05).\n Educating women about clinical trials in this manner appears ineffective in improving recruitment to RCTs. Women appear to be more influenced by their perception of risk than understanding. This finding has ethical implications for communication of information about RCTs.", "A prospective, randomized study was performed to determine the efficacy of neoadjuvant chemotherapy over radiotherapy alone in patients with locally advanced nasopharyngeal carcinoma.\n From January 1991 to December 1998, 80 patients were enrolled in this study. Patients with locoregional carcinoma of the nasopharynx were randomized to receive two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil (CDDP-5FU), that were administered before radiation therapy (CT arm) or radiotherapy alone. The patients who received neoadjuvant chemotherapy were treated with radiation therapy, which was scheduled to commence 2 weeks after the second course chemotherapy.\n With a median follow-up of 49 months, a trend toward improved overall survival or disease free survival favoring the CT arm was observed (5-year overall survival rate, 60% vs. 48%; 5-year disease free survival rate, 55% vs. 43%), although this difference was not significant. There were no differences in locoregional failure free survival between the two arms. However, metastasis free survival favored the CT arm, although this difference was not significant. The results also demonstrated that most patients in the CT arm who experienced recurrent disease developed locoregional recurrences before distant metastases, suggesting that improvements in locoregional control may lead to improved disease free survival.\n The use of CDDP-5FU chemotherapy prior to radiotherapy in patients with nasopharyngeal carcinoma did not result in a significant improvement in disease free survival or overall survival. However, there was a positive tendency in favor of the CT arm for distant metastasis free survival, although there was no improvement in the locoregional recurrence free survival rate.\n Copyright 2002 American Cancer Society.", "A first breast cancer recurrence creates considerable distress, yet few psychosocial interventions directed at this population have been reported. The Southwest Oncology Group conducted a phase III randomized trial to evaluate the effectiveness of a brief telephone intervention.\n Three hundred five women experiencing a first recurrence of breast cancer were randomly assigned to standard care or intervention. The intervention consisted of four to eight telephone calls delivered over a 1-month period. The calls were conducted by trained peer counselors at a breast cancer advocacy organization, the Y-ME National Breast Cancer Organization, and followed a standard curriculum. Psychosocial distress (Cancer Rehabilitation Evaluation System-Short Form [CARES-SF]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) outcomes were assessed at baseline and 3 and 6 months. The 3-month assessment was the primary end point and is the focus of this article.\n Analysis revealed no differences in distress or depressive symptoms at 3 months between the intervention and control groups; at 3 months, 70% of control patients and 66% of intervention patients reported psychosocial distress, and 40% of control patients and 47% of intervention patients exhibited depressive symptoms.\n Telephone peer counseling did not lead to better psychosocial outcomes. The persistent distress in these women supports the urgent need for the development and testing of more intensive or different supportive interventions for this group of patients.", "Between June 1975 and April 1981, 61 of the 177 eligible patients whose nonosseous sarcomas of extremity or trunk origin had been completely excised primarily or after local recurrences agreed to participate in a randomized study of adjuvant chemotherapy. Dermatofibrosarcoma, lymphomas, myeloma, Kaposi's sarcoma, and embryonal rhabdomyosarcoma were excluded as were patients with significant second primary cancers and those who received either preoperative or postoperative radiation therapy. After stratification by anatomic status of disease, site of origin, and histologic grade, a random one half of the 61 participants began alternating courses of vincristine/cyclophosphamide/dactinomycin, and vincristine/doxorubicin/dacarbazine at six-week intervals for one year. The control group was evaluated at six-week intervals without adjuvant chemotherapy, but these patients were offered this chemotherapy later if they had progressive disease excised. Although 30% of the 61 patients experienced local recurrence of disease within the first five years after randomization, and only 54% were continuously disease free for five or more years, 82% were surviving at five years (Kaplan-Meier calculations) with a median follow-up of 64.3 months. Partial suppression of distant metastasis by adjuvant chemotherapy was apparent in the overall study, in the extremity tumor category, and in the subgroup of patients who had received limb-sparing surgery; however, no survival advantage for chemotherapy-treated patients was demonstrated. The 30 adjuvant chemotherapy-treated patients received a total of three thoracotomies as compared with 17 salvage thoracotomies for the 31 control patients; however, salvage surgery for local recurrences has been similar in the two groups. Recent improvement in the survival of patients with soft-tissue sarcomas is not necessarily a result of adjuvant chemotherapy or radiation therapy.", "Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled.\n Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy.\n In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01).\n Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.\n Copyright 2010 Elsevier Ltd. All rights reserved." ]

[ "12964289", "1356466", "17456554", "12216046", "12712026", "14974959", "7212184", "10085281", "10734596" ]

[ "Is tap water a safe alternative to normal saline for wound irrigation in the community setting?", "Comparison between sterile saline and tap water for the cleaning of acute traumatic soft tissue wounds.", "A multicenter comparison of tap water versus sterile saline for wound irrigation.", "Tap water for irrigation of lacerations.", "Wound irrigation in children: saline solution or tap water?", "Bacterial load in relation to vacuum-assisted closure wound therapy: a prospective randomized trial.", "Effect of washing closed head and neck wounds on wound healing and infection.", "Effects of topical honey on post-operative wound infections due to gram positive and gram negative bacteria following caesarean sections and hysterectomies.", "[Modification of postoperative wound healing by showering]." ]

[ "This double-blind randomised controlled trial compared the effects of tap water and normal saline on the healing and infection rates of acute and chronic wounds.\n The trial was conducted in two metropolitan community health centres in New South Wales, Australia. Thirty-five patients with 49 acute or chronic wounds were randomised to receive wound irrigation with either normal saline or tap water.\n Statistical analysis demonstrated there was no significant difference between the infection and healing rates in wounds irrigated with normal saline or tap water.\n Although the small sample size is a limitation of this study, the researchers conclude that drinkable tap water appears to provide a safe alternative to normal saline for wound cleansing and may be preferred by some patients.", "To find out if there were any differences in infection rates if acute traumatic soft tissue wounds were cleaned with tap water instead of sterile saline.\n Randomised study.\n Emergency department at one city hospital.\n 705 consecutive patient with soft tissue wounds less than six hours old that did not penetrate a viscus, cavity, or joint and could be treated by primary suture.\n Randomly allocated to have the wound cleaned with either sterile saline or tap water in addition to debridement.\n Rate of wound infection, the presence of which was indicated by pus in the wound and prolonged healing.\n The infection rate in wounds cleaned with sterile saline was 10.3% compared with 5.4% in wounds cleaned with tap water (p less than 0.05). Infected wounds were significantly larger than uninfected ones (p less than 0.05) and more likely to be located on a lower extremity (p less than 0.05). There were no microbiological differences between the two groups, and no bacterial species grown from tap water was subsequently grown from an infected wound.\n Sterile saline should be replaced by tap water for the cleaning of acute traumatic superficial soft tissue wounds.", "To compare wound infection rates for irrigation with tap water versus sterile saline before closure of wounds in the emergency department.\n The study was a multicenter, prospective, randomized trial conducted at two Level 1 urban hospitals and a suburban community hospital. Subjects were a convenience sample of adults presenting with acute simple lacerations requiring sutures or staples. Subjects were randomized to irrigation in a sink with tap water or with normal saline using a sterile syringe. Wounds were closed in the standard fashion. Subjects were asked to return to the emergency department for suture removal. Those who did not return were contacted by telephone. Wounds were considered infected if there was early removal of sutures or staples, if there was irrigation and drainage of the wound, or if the subject needed to be placed on antibiotics. Equivalence of the groups was met if there was less than a doubling of the infection rate.\n A total of 715 subjects were enrolled in the study. Follow-up data were obtained on 634 (88%) of enrolled subjects. Twelve (4%) of the 300 subjects in the tap water group had wound infections, compared with 11 (3.3%) of the 334 subjects in the saline group. The relative risk was 1.21 (95% confidence interval = 0.5 to 2.7).\n Equivalent rates of wound infection were found using either irrigant. The results of this multicenter trial evaluating tap water as an irrigant agree with those from previous single institution trials.", "This study was designed to compare the infection rates of simple lacerations irrigated with tap water versus sterile normal saline before repair. Patients with simple lacerations to an extremity that were less than 8 hours from injury were prospectively enrolled. Exclusions from the study were: dog bites, hand lacerations, immunocompromised patients, and those on antibiotics at the time of injury. Patients who qualified were randomized to receive tap water or normal saline for wound irrigation. Before and after irrigation, wound cultures were obtained. After the procedure was complete, patients were scheduled for a 48 hour follow-up wound check. A total of 46 patients were enrolled in the study. Twenty-four patients were randomized to the normal saline group and 21 were assigned to receive tap water irrigation. There were 2 infected lacerations in both the tap water and normal saline groups. The organisms cultured from the wounds in both groups were similar and there was no difference in colony counts when tap water was used. The use of tap water for the irrigation of lacerations does not result in the growth of unusual organisms or increase the colony counts of organisms. Wound infection rates were the same in both groups. This pilot study suggests that the use of tap water for irrigation of wounds may be safe. Further validation is necessary.\n Copyright 2002, Elsevier Science (USA). All rights reserved.", "Irrigation, a critical component of wound management, is commonly performed with sterile normal saline solution. The purpose of this study was to compare the infection rates of wounds irrigated with normal saline solution versus those of wounds irrigated with running tap water.\n A prospective trial was conducted in an urban pediatric emergency department. Tap water pressure and flow rates were measured, and cultures were obtained before the study and at 5 months after study initiation. Patients 1 to 17 years of age presenting to the pediatric ED with a simple laceration were eligible. Exclusion criteria included immunocompromise, complicated lacerations, or current use of or need for antibiotics. Patients were allocated to the running tap water group or the standard normal saline solution irrigation group. Wounds were closed in standard fashion. Patients returned to the pediatric ED in 48 to 72 hours for evaluation.\n Two hundred seventy-one patients were enrolled in the normal saline solution group and 259 in the tap water group. Tap water and normal saline solution pressures and flow rates differed. The groups did not differ in terms of patient demographic characteristics or wound characteristics. However, more wounds were located on the hand in the tap water group (21.3%; 95% confidence interval [CI] 16.3% to 27.1%) compared with those in the normal saline solution group (9.2%; 95% CI 5.9% to 13.4%). The wound infection rates were similar in the 2 groups (normal saline solution group: 2.8% [95% CI 1.1% to 5.7%] versus running tap water group: 2.9% [95% CI 1.2% to 5.9%]).\n There were no clinically important differences in infection rates between wounds irrigated with tap water or normal saline solution. Tap water might be an effective alternative to normal saline solution for wound irrigation in children.", "Vacuum-assisted closure has become a new technique in the challenging management of contaminated, acute, and chronic wounds. Although promising clinical results have been described, scientific proof to substantiate the mechanism of action of this therapy is scarce. In the present study, we examined whether the positive effect on wound healing found in vacuum-assisted closure-treated wounds could be explained by an effect on the bacterial load. Fifty-four patients who needed open wound management before surgical closure were included in this study. Wounds were randomized to either vacuum-assisted closure therapy (n= 29) or treatment by conventional moist gauze therapy (n= 25). Healing was characterized by development of a clean granulating wound bed (\"ready for surgical therapy\") and reduction of wound surface area. To quantify bacterial load, biopsies were collected. No significant difference was found in time needed to reach \"ready for surgical therapy\" comparing both therapies. Wound surface area reduction was significantly larger in vacuum-assisted closure-treated wounds: 3.8 +/- 0.5 percent/day (mean +/- SEM) compared to conventional-treated wounds (1.7 +/- 0.6 percent/day; p < 0.05). The total quantitative bacterial load was generally stable in both therapies. However, nonfermentative gram negative bacilli showed a significant decrease in vacuum-assisted closure-treated wounds (p < 0.05), whereas Staphylococcus aureus showed a significant increase in vacuum-assisted closure-treated wounds (p < 0.05). In conclusion, this study shows a positive effect of vacuum-assisted closure therapy on wound healing, expressed as a significant reduction of wound surface area. However, this could not be explained by a significant quantitative reduction of the bacterial load.", "A group of 100 patients were compared with 100 control patients. Both groups had either traumatic or surgically incised clean wounds of the head and neck. The groups were similar except that the 100 test patients were allowed to wash their head and neck wounds with soap and water within hours after the repair, while the control group kept their wounds dry until all of the sutures were removed. On the basis of this study, we believe that allowing patients to wash their wounds and bathe routinely as early as 8 hours after wound closure hs no effect on wound or infection. We believe that good technique during surgery for incision or laceration closure is much more important than any manipulation of the wound or of the general body systems.", "The possible therapeutic effect of topical crude undiluted honey in the treatment of severe acute postoperative wound infections was studied. Fifty patients having postoperative wound infections following caesarean sections or total abdominal hysterectomies with gram positive or gram negative bacterial infections were allocated in two groups. Twenty-six patients (group A) were treated with 12 hourly application of crude honey and 24 patients (group B) were treated with local antiseptics: spirit (70% Ethanol) and povidone-iodine. Both groups received systemic antibiotics according to culture and sensitivity. Results showed that eradication of bacterial infections was obtained after 6 +/- 1.9 days (mean +/- SD) in group A and after 14.8 +/- 4.2 days in group B (p <0.05). Period for antibiotics use was 6.88 +/- 1.7 days in-group A and 15.45 +/- 4. 37 in-group B (p <0.05). Complete wound healing was evident after 10. 73 +/- 2.5 days in group A and after 22.04 +/- 7.33 in group B (p <0. 05). Size of postoperative scar was 3.62 +/- 1.4 mm after using topical honey and was 8.62 +/- 3.8 mm after local antiseptics (p <0. 05). The mean hospital stay was 9.36 +/- 1.8 days in group A and 19. 91 +/- 7.35 days in group B (p <0.05). After using honey, 22/26 patients (84.4%) showed complete wound healing without wound disruption or need for re-suturing and only 4 patients showed mild dehiscence. In group B, 12/24 patients (50%) showed complete wound healing and 12 patients showed wound dehiscence, six of them needed re-suturing under general anesthesia. We concluded that topical application of crude undiluted honey could (1) faster eradication of bacterial infections, (2) reduce period of antibiotic use and hospital stay, (3) accelerate wound healing, (4) prevent wound dehiscence and need for re-suturing and (5) result in minimal scar formation.", "Usually postoperative wounds are kept dry until the stitches are removed. In a prospective randomized study early water contact was allowed in order to test postoperative wound healing in 817 patients operated on for varicose veins. Regardless of whether the wounds were kept dry or had water contact with or without shower foam from the second postoperative day, no infection was registered." ]

[ "2668784", "8549944", "1638191", "10925979", "7502549", "3319461", "10102971", "11227650", "2577483" ]

[ "A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.", "A controlled double blind study of azathioprine in the management of Crohn's disease.", "Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.", "Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis.", "Comparison between high dose 5-aminosalicylic acid and 6-methylprednisolone in active Crohn's ileocolitis. A multicenter randomized double-blind study. German 5-ASA Study Group.", "Double-blind, placebo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using 99mTc-labeled 5-ASA suppositories.", "Is maintenance therapy always necessary for patients with ulcerative colitis in remission?", "[Azathioprine and 5-ASA in the prevention of postoperative recurrence of Crohn's disease].", "Comparative efficacy of coated, oral 5-aminosalicylic acid (Claversal) and sulphasalazine for maintaining remission of ulcerative colitis. International Study Group." ]

[ "Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose \"pulse\" and alternate-day regimen. The \"intent-to-treat\" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.", "While immunosuppressive agents are used widely in the management of Crohn's disease, their efficacy has not been well established in randomised controlled trials. This study was designed to examine whether azathioprine increases remission rate when used in conjunction with a diminishing dose regimen of prednisolone over a period of 12 weeks. It further examined whether azathioprine offers any therapeutic advantage over placebo in the maintenance of remission in Crohn's disease over a period of 15 months. Sixty three patients with active Crohn's disease were treated with a 12 weeks diminishing dose of prednisolone and at the same time entered into a randomised, double blind 15 month trial of either azathioprine (2.5 mg/kg) or placebo. Remission rates between the two groups were compared at 12 weeks and at 15 months. There was no significant difference in the proportion of patients who had achieved and maintained remission by week 12 but at 15 months there was a highly significant difference in the proportion of patients in remission (42% receiving azathioprine v 7% receiving placebo), p = 0.001. Using life tables this beneficial effect was reflected as the difference in the median number of days on the trial (p = 0.02). There were significantly greater decreases over the trial period in the median erythrocyte sedimentation rate, C reactive protein, and leucocyte count in the azathioprine group. There were no cases of severe bone marrow suppression or clinical pancreatitis. In conclusion, azathioprine offers a therapeutic advantage over placebo in the maintenance of remission in Crohn's disease.", "To determine whether azathioprine can prevent relapse in ulcerative colitis.\n One year placebo controlled double blind trial of withdrawal or continuation of azathioprine.\n Outpatient clinics of five hospitals.\n 79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo.\n Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance.\n For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal.\n Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.", "The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission.\n In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy).\n Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events.\n The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis.", "The value of 5-aminosalicylic acid (5-ASA) in Crohn's disease (CD) is still under discussion. In a previous study 2 g 5-ASA per day were inferior to a standard glucocorticoid treatment with 6-methylprednisolone (6-MPred) (Can J Gastroenterol 1990; 4: 446-51). In the present study we tested whether in active CD response rates to 4.5 g 5-ASA/day were not different from those to 6-MPred.\n Multicenter randomized double-blind double-dummy trial. 34 patients with active CD (CDAI > 150) were included. 17 patients were in the 5-ASA group (Salofalk, 4.5 g/day), 17 patients in the 6-MPred group (Urbason, initial dose 48 mg/day, weekly tapering). Duration of treatment was 8 weeks. Main outcome measure was remission of CD (CDAI < 150) and decrease of at least 60 points.\n Both groups were comparable with respect to demographic and clinical parameters. The median CDAI decrease in the 5-ASA group was 85, in the 6-MPred group 122 (p = 0.7437). The median AUC of the CDAI in the 5-ASA group was 1027, in the 6-MPred group 950 (p = 0.137). The median AUC of the CDAI per treatment day was 22.94 in the 5-ASA group, and 17.33 in the 6-MPred group (p = 0.0555). On an intention-to-treat basis remission rates after 8 weeks were 40.0% in the 5-ASA group and 56.3% in the 6-MPred group (p = 0.5867).\n Response rates to 5-ASA or 6-MPred were not significantly different although there was a trend towards a higher efficacy of 6-MPred. 5-ASA may be considered as alternative treatment in patients with activer CD who are intolerant to or refuse glucocorticoids.", "Patients with active distal proctitis received either 5-aminosalicylic (5-ASA) acid or identical placebo suppositories, 500 mg t.i.d. for 6 weeks. Activity at 3 and 6 wks was assessed using a Disease Activity Index (DAI), derived from four categories: number of daily evacuations more than usual, evacuations containing blood, sigmoidoscopy appearance, and physician's overall assessment. Each category was graded 0-3. There was thus 0-12 points scored ranging from complete remission to severe disease. A minimum score of 3 from two categories was necessary for study entry. Of 27 patients randomized, 14 received active medication and 13 placebo. Of the 14 patients, with initial mean DAI 7.1 +/- 1.8, 11 were in complete remission at 6 wks (78.6%). Whereas, there was no significant change in the placebo group, with initial mean DAI 7.1 +/- 1.8. An additional 6 patients with inflammatory bowel disease and 6 healthy volunteers were given 99mTc-labelled 5-aminosalicylic acid suppositories. The extent of spread was limited to the rectum, and the suppositories were retained for 3 hours. There was no absorbed radioactivity. 5-ASA suppositories are safe, well-tolerated, and effective treatment for active distal proctitis.", "The efficacy of sulphasalazine and mesalazine in preventing relapse in patients with ulcerative colitis is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence.\n To determine whether the duration of disease remission affects the relapse rate, by comparing the efficacy of a delayed-release mesalazine (Asacol, Bracco S.p.A., Milan, Italy) against placebo in patients with ulcerative colitis with short- and long-duration of disease remission.\n 112 patients (66 male, 46 female, mean age 35 years), with intermittent chronic ulcerative colitis in clinical, endoscopic and histological remission with sulphasalazine or mesalazine for at least 1 year, were included in the study. Assuming that a lower duration of remission might be associated with a higher relapse rate, the patients were stratified according to the length of their disease remission, prior to randomization into Group A (Asacol 26, placebo 35) in remission from 1 to 2 years, or Group B (Asacol 28, placebo 23) in remission for over 2 years, median 4 years. Patients were treated daily with oral Asacol 1.2 g vs. placebo, for a follow-up period of 1 year.\n We employed an intention-to-treat analysis. In Group A, whilst no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months [Asacol 6/26 (23%), placebo 17/35 (49%), P = 0.035, 95% Cl: 48-2.3%]. In contrast, in Group B no statistically significant difference was observed between the two treatments, either at 6 or 12 months [Asacol 5/28 (18%), placebo 6/23 (26%), P = 0.35, 95% Cl: 31-14%] of follow-up. Patients in group B were older, and had the disease and remission duration for longer, than those in Group A.\n Mesalazine prophylaxis is necessary for the prevention of relapse by patients with ulcerative colitis in remission for less than 2 years, but this study casts doubt over whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic and histological remission, who are at very low risk of relapse.", "Recurrence of Crohn's disease (CD) lesions in the neo-ileum after apparently curative resection frequently occurs after surgery. The most appropriate prophylactic treatment has not been clearly defined. This study evaluated the efficacy of 5-ASA and azathioprine in decreasing postoperative recurrence and analysed the presence of variables associated with recurrence. Thirty-nine patients (mean age 32.8 years, range 18-61) with a history of ileal or ileocecal surgical resection were studied. They received 5-ASA (3 mg/day) or azathioprine (50 mg/day) immediately after the operation and for 2 years thereafter. Patients were followed clinically (Crohn's disease activity index) and serologically every 3 months and by imaging methods every 6 months. The latter included colonoscopy with ileoscopy and if not available, small bowel barium or ultrasonographic study. Laboratory tests included ESR, C-reactive protein, white blood cell and platelet count, fibrinogen and albumin. The end-point evaluated included clinical recurrence (CR), serological recurrence (SR: alteration of at least three of the above-mentioned variables) and morphologic recurrence (MR: endoscopic recurrence > 1 according to Rutgeerts score or radiological or ultrasonographic recurrence). Eighteen patients received azathioprine and 21 received 5-ASA. Thirty-four patients were evaluated. The cumulative proportion of patients with recurrence was 29% (CR), 35% (SR) and 50% (MR). Statistical analysis did not show significant differences between the two groups. Twenty-seven patients completed the 2-year study (11 in the azathioprine group and 16 in the 5-ASA group). Crude relapse rates were 37% (CR), 44% (SR) and 69% (MR) in the 5-ASA group and 36% (CR), 45% (SR) and 64% (MR) in the azathioprine group. No statistically significant differences were observed between groups. No variables associated with recurrence were detected. In conclusion, treatment does not prevent a high percentage of postsurgical recurrence. 5-ASA (3 g/day) and azathioprine (50 mg/day) showed similar efficacy in the prevention of recurrence.", "The safety and efficacy of Claversal (coated, oral 5-aminosalicylic acid (5-ASA) 0.75 g/day) and sulphasalazine 1.5-2.0 g/day were compared for the maintenance treatment of ulcerative colitis in a 1-year double-blind trial. Three hundred and thirty-four patients, whose disease was controlled on a stable dose of sulphasalazine (1.5-2.0 g/day) for a 1-month pre-trial, entered the study. On entry, patients were assigned in a random manner to continue sulphasalazine or to switch to coated 5-ASA. One hundred and thirty-one patients in the coated 5-ASA group and 142 on sulphasalazine were analysed for efficacy. No significant difference was observed between treatments with respect to the cumulative rate of relapse. Over the 12 months, 30 (28%) of the coated 5-ASA patients versus 29 (23%) of those treated with sulphasalazine had an exacerbation of their disease (log rank test P = 0.7011). The incidence of drug-related adverse events and subsequent withdrawals was similar. The high incidence of side-effects usually associated with sulphasalazine was not observed, probably due to the fact that this population was tolerant of sulphasalazine pre-trial. Of the 37 patients who reported adverse events with previous sulphasalazine therapy, however, only two (8%) of the 24 experienced those events when randomized to coated 5-ASA while five (38%) of the 13 who continued on sulphasalazine reported those same events. Coated 5-ASA is a safe, effective therapy for maintaining ulcerative colitis in remission." ]

[ "2847578", "7606516", "2536255", "2847600", "8412049", "2852903", "2167369", "3027153", "1310834" ]

[ "Effect of nedocromil sodium on exercise-induced bronchoconstriction in children.", "Effect of nedocromil sodium on exercise-induced bronchoconstriction exacerbated by inhalation of cold air.", "Nedocromil sodium in exercise-induced bronchoconstriction in children.", "A comparative study of the effect of three doses of nedocromil sodium and placebo given by pressurized aerosol to asthmatics with exercise-induced bronchoconstriction.", "Nedocromil sodium in the prevention of exercise-induced bronchospasm in athletes with asthma.", "A comparative study of the effects of two different doses of nedocromil sodium and placebo given by pressurised aerosol in exercise-induced bronchoconstriction.", "Attenuation of exercise induced asthma by nedocromil sodium and sodium cromoglycate.", "The preventive effect and duration of action of nedocromil sodium and cromolyn sodium on exercise-induced asthma (EIA) in adults.", "Effects of nedocromil sodium, cromolyn sodium, and a placebo in exercise-induced asthma." ]

[ "A double-blind, placebo-controlled, crossover study investigated the efficacy of nedocromil sodium in reducing bronchoconstriction subsequent to exercise challenge in asthmatic children. Twelve children aged 7-14 years (mean 10.8 years) were pretreated with nedocromil sodium aerosol (2 inhalations; 2 mg/inhalation) or matching placebo, 30 min prior to treadmill running. Lung function was measured at regular intervals postexercise and the mean maximum percentage decrease in PEF and FEV1 compared following nedocromil sodium or placebo pretreatment. Nedocromil sodium significantly reduced the fall in PEF (P less than 0.001) and FEV1 (P less than 0.001) and provided significantly greater protection (P less than 0.001) than placebo. No adverse reactions or unusual symptoms were observed.", "This double-blind placebo-crossover study examined the effect of nedocromil sodium, 4 mg aerosol 30 min before challenge, on exercise-induced bronchoconstriction (EIB) in cold air conditions. Twenty-one asthmatic patients (15-28 years), with methacholine PC20 < or = 8 mg/ml in the absence of significant allergen exposure, were randomized to active and placebo therapy on separate study days. Pulmonary function, measured up to 20 min after exercise, showed significantly less deterioration with nedocromil sodium, which effectively halved the maximum percentage decline in forced expiratory volume in the first second. EIB was increased by cold air, whereas an ancillary study in 15 healthy volunteers (18-19 years) showed no such effects. We conclude that prior inhalation of nedocromil sodium diminished cold air-exacerbated EIB in young adult asthmatic patients.", "Twenty asthmatic children were studied in a double-blind within-patient comparative trial designed to assess the efficacy of nedocromil sodium (4 mg) and placebo in exercise-induced bronchoconstriction. The response to exercise challenge given 30 minutes after treatment showed statistically significant differences in favor of nedocromil sodium. No unusual symptoms were reported.", "The effect of placebo and 1 mg, 4 mg, or 8 mg nedocromil sodium, administered 60 minutes prior to treadmill challenge, was determined in a double-blind study of 12 adult asthmatics with reproducible exercise-induced bronchoconstriction. All nedocromil sodium treatments gave significantly smaller falls in PEFR than placebo. Four and 8 mg gave significantly greater protection than 1 mg.", "The aim of this study was to determine the efficacy of nedocromil sodium in the prevention of exercise-induced bronchospasm (EIB) in 13 top athletes affected by bronchial asthma. At a dose of 4 mg the drug significantly reduced the fall in FEV1 compared with placebo but not with respect to basal values. In 9 athletes, 4 mg nedocromil sodium produced a good protective effect and reduced the mean fall in FEV1 to 4% with respect to baseline values, while in the remaining 4 subjects, the protective effect was not satisfactory. In these 4 \"non responders\" 6 mg nedocromil was effective, and in 2 cases induced prolonged bronchodilatation. In conclusion, the effect of nedocromil sodium in the prevention of EIB may be dose-dependent in relation to the degree of bronchial hyperreactivity or to interference of other factors.", "Fourteen adult subjects with stable asthma were treated using a double-blind crossover, randomised protocol, with either nedocromil sodium (4 mg or 2 mg) or placebo. The agents were administered from matched pressurised aerosol inhalers 30 min before exposure to an exercise regimen which, on a previous screening day, resulted in a 24-53% (mean: 33.9%) decrease in peak expiratory flow (PEF). Both doses of nedocromil sodium were significantly superior to placebo in preventing the exercise-induced decrease in PEF and were without side effects. This study confirms and extends the results of earlier trials with nedocromil sodium and further supports the contention that this new agent may be of benefit in the treatment of reversible obstructive airways disease in the adult patient.", "A randomized double blind cross over trial to compare nedocromil sodium and sodium cromoglycate with placebo in the prevention of exercise induced asthma was conducted. Twenty asthmatics received nedocromil sodium, sodium cromoglycate or placebo via metered dose inhalers on successive days 30 minutes before exercise in a randomized order. Nedocromil sodium and sodium cromoglycate gave sufficient protection (P less than 0.05) compared to placebo as assessed by the reduction in the maximum percentage fall in the forced expiratory volume in 1 second (FEV1). The protective effect of nedocromil sodium and sodium cromoglycate varied in individuals.", "Nedocromil sodium, 4 mg, from a metered-dose inhaler, cromolyn sodium, (cr) 20 mg, from a Spinhaler, and placebo (pl) were compared in their efficacy and duration of action in preventing exercise-induced asthma. Twelve patients with asthma performed treadmill exercise tests 20 minutes, 2 hours, and 4 hours after a single dose of drug in a double-blind, crossover trial. Both active drugs were significantly better than pl at 20 minutes. Two hours after drug administration, only cr was significantly different from pl. The direct comparison between nedocromil and cr demonstrated no significant difference on FEV1, and the only significant difference was with forced expiratory flow between 25% and 75% of vital capacity at 2 hours. It is concluded that at these clinically recommended doses, both drugs are equally effective in preventing exercise-induced asthma with cr possibly having a somewhat longer duration of action.", "The incidence and severity of exercise-induced asthma were determined in nineteen asthmatic patients who performed eight minutes of exercise following four treatments administered in a random order. The treatments were nedocromil sodium, cromolyn sodium, placebo, and no treatment. It was concluded that nedocromil sodium (8 mg) and cromolyn sodium (4 mg) provide equal protection against exercise-induced asthma." ]

[ "11768836", "16267634", "16062094", "16889453", "17728106", "16585435", "16585434", "16797162", "12766921" ]

[ "A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: the quetiapine experience with safety and tolerability (QUEST) study.", "Quetiapine has equivalent efficacy and superior tolerability to risperidone in the treatment of schizophrenia with predominantly negative symptoms.", "Risperidone, quetiapine, and fluphenazine in the treatment of patients with therapy-refractory schizophrenia.", "Comparison of quetiapine and risperidone in the treatment of schizophrenia: A randomized, double-blind, flexible-dose, 8-week study.", "Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine.", "Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.", "A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization.", "The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia." ]

[ "The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice.\n The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms.\n This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D).\n A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028).\n The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability.", "Atypical antipsychotics are generally thought to be more effective than conventional agents in treating the negative symptoms of schizophrenia; however, there have been few direct comparisons among atypicals. We therefore investigated risperidone and quetiapine with respect to their efficacy against negative symptoms in a 12-week,double-blind, comparative pilot study involving 44 patients with schizophrenia with predominantly negative symptoms, as defined by Positive and Negative Syndrome Scale (PANSS) scores. Other efficacy measures included the Scale for the Assessment of Negative Symptoms (SANS) and the Clinical Global Impression (CGI) rating scale. Antipsychotic tolerability was assessed using the Simpson-Angus Scale (SAS) and various laboratory measures. Mean doses were 589.7 mg/ day quetiapine and 4.9 mg/day risperidone (observed cases). Both antipsychotics produced significant decreases in PANSS total, positive and negative scores, and SANS scores. Patients receiving risperidone were significantly more likely to experience extrapyramidal symptoms (EPS) [p <0.05], or to require anticholinergic medication (p <0.05), and had significantly higher prolactin levels (p <0.001) than quetiapine-treated patients. In conclusion, there is no significant difference in efficacy between quetiapine and risperidone in alleviating the negative symptoms of schizophrenia. Quetiapine is also well tolerated, with a lower incidence of EPS and prolactin increase than risperidone.", "This 12-week, double-blind study evaluated the effectiveness of risperidone (4 mg/day), quetiapine (400 mg/day), or fluphenazine (12.5 mg/day) in a stringently defined treatment-resistant population of people with schizophrenia. No differences were noted in total Brief Psychiatric Rating Scale (BPRS) or Clinical Global Impression scores among the drug groups (n = 38). More subjects tended to complete the study on risperidone (69%) or quetiapine (58%) than those treated with fluphenazine (31%; P value not significant). Eighty-nine percent of those who discontinued on fluphenazine (8 of 9) were due to lack of efficacy. Discontinuation due to adverse effects was low, with only 2 subjects (both on quetiapine) stopping due to side effects. Three of 13 risperidone-treated subjects (23%) and 3 of 12 quetiapine-treated subjects (25%) met response criteria (decrease of 20% of total BPRS score), whereas 2 of 13 subjects (15%) responded to fluphenazine. Side effect occurrence was similar among drug groups and EPS ratings on the Simpson Angus Scale improved in all drug groups (quetiapine, 1.64; risperidone, 1.30; fluphenazine, 0.69; P value not significant). Despite the newer class of second-generation antipsychotic medications, this treatment-resistant population remains difficult to treat. Many people have only minimal to modest improvements with antipsychotic treatment and most continue to have residual psychotic symptoms. Treatment with first- and second-generation antipsychotics may demonstrate similar efficacy; however, patients treated with second-generation antipsychotics may be more likely to adhere to treatment.", "To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia.\n In this 8-week, double-blind, multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis) were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8 mg/day). The primary hypothesis was that quetiapine was not inferior to risperidone. The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression-Change (CGI-C), and cognitive and social functioning. Tolerability assessments included treatment-emergent adverse events and changes in weight, glucose, and prolactin. Patients were recruited from June 2001 to September 2002.\n Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525 mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis demonstrated noninferiority between treatments (p < .05). Improvements with both treatments were comparable on PANSS total, negative, and general psychopathology subscales. Risperidone-treated patients had a significantly (p = .03) greater improvement in PANSS positive subscale score among all patients, but not among completers. Improvements in PANSS response rates, CGI-C, and cognitive function were similar between treatment groups. Changes in serum glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001).\n Quetiapine and risperidone had broadly comparable clinical efficacy. Both agents improved cognitive and social functioning, and neither had a clinically significant effect on weight or glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin rates were significantly higher with risperidone.", "Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure.\n The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia.\n In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI).\n Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life.\n Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities.", "In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic.\n Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason.\n The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168).\n Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.", "When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.\n Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).\n Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.\n For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.", "This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization.\n This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications.\n Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain.\n While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.", "Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design.\n To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone.\n Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted.\n 66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure.\n After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.\n Copyright 2003 John Wiley & Sons, Ltd." ]

[ "19926959", "18564353", "18770876", "17031321", "17984757", "19418715", "20081394", "17713983", "18753864" ]

[ "A cluster-randomized trial of enhanced labor ward-based PMTCT services to increase nevirapine coverage in Lusaka, Zambia.", "Quality of antenatal and delivery care before and after the implementation of a prevention of mother-to-child HIV transmission programme in Côte d'Ivoire.", "The impact of scaling-up prevention of mother-to-child transmission (PMTCT) of HIV infection on the human resource requirement: the need to go beyond numbers.", "Integration of antiretroviral treatment within antenatal care in Gauteng Province, South Africa.", "Do targeted HIV programs improve overall care for pregnant women?: Antenatal syphilis management in Zambia before and after implementation of prevention of mother-to-child HIV transmission programs.", "Improving quality of prevention of mother-to-child HIV transmission services in Ukraine: a focus on provider communication skills and linkages to community-based non-governmental organizations.", "The use of routine monitoring and evaluation systems to assess a referral model of family planning and HIV service integration in Nigeria.", "Antiretroviral treatment and prevention of peripartum and postnatal HIV transmission in West Africa: evaluation of a two-tiered approach.", "Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Côte d'Ivoire." ]

[ "Determine whether enhanced labor ward-based services for prevention of mother-to-child transmission of HIV (PMTCT) would improve nevirapine (NVP) coverage.\n Cluster-randomized trial at 12 public-sector delivery centers in Lusaka, Zambia.\n Following a baseline surveillance period, 12 labor wards were randomized, six to offer opt-in HIV testing to women of unknown serostatus (with NVP administration as indicated) and to assess NVP adherence among known HIV-infected women. The six control labor wards provided the standard of care. The NVP coverage endpoint was defined as the proportion of HIV-infected/exposed women/infant pairs with confirmed NVP ingestion. We used generalized estimating equations (GEE) to determine the odds of coverage associated with the intervention and ultimately used the parameters for the estimated GEE model to estimate relative risk.\n Between October 2005 and January 2006, 7664 women gave birth at participating clinics. We collected anonymous-linked blood from 7592 (99%) umbilical cords; tested 7438 (97%) for HIV, 1618 (22%) were seropositive, and of these, 1279 (79%) were tested for NVP. At baseline (preintervention), the probability of HIV-infected/exposed women/infant pairs receiving NVP in treatment clinics (42%) was 0.89 times the probability of being covered in control clinics (53%) whereas during the intervention period the probability of treatment clinic coverage (52%) was 1.22 the probability control clinic coverage (43%), representing a multiplicative effect of 1.37 upon the RR at baseline (ratio of relative risks 1.37, bootstrapped 95% CI, 1.04-1.77).\n Labor ward-based PMTCT programs are feasible and can have a significant, positive impact on NVP coverage.", "To assess whether implementation of a prevention of mother-to-child HIV transmission (PMTCT) programme in Côte d'Ivoire improved the quality of antenatal and delivery care services.\n Quality of antenatal and delivery care services was assessed in five urban health facilities before (2002-2003) and after (2005) the implementation of a PMTCT programme through review of facility data; observation of antenatal consultations (n = 606 before; n = 591 after) and deliveries (n = 229 before; n = 231 after) and exit interviews of women; and interviews of health facility staff.\n HIV testing was never proposed at baseline and was proposed to 63% of women at the first ANC visit after PMTCT implementation. The overall testing rate was 42% and 83% of tested HIV-infected pregnant women received nevirapine. In addition, inter-personal communication and confidentiality significantly improved in all health facilities. In the maternity ward, quality of obstetrical care at admission, delivery and post-partum care globally improved in all facilities after the implementation of the programme although some indicators remained poor, such as filling in the partograph directly during labour. Episiotomy rates among primiparous women dropped from 64% to 25% (P < 0.001) after PMTCT implementation. Global scores for quality of antenatal and delivery care significantly improved in all facilities after the implementation of the programme.\n Introducing comprehensive PMTCT services can improve the quality of antenatal and delivery care in general.", "Although the mother-to-child transmission (MTCT) contributes only 5% of transmission of HIV infection, its impact has reversed the decline in infant and child mortality rates. With antenatal service coverage of over 90%, the integration of prevention of MTCT (PMTCT) of HIV infection into the Reproductive and Child Health (RCH) services in Tanzania, this is likely to overstretch the staff capacity and undermine the already compromised quality of health care services. A retrospective study was conducted to assess the impact of integrating and scaling-up PMTCT of HIV infection into routine RCH services, on the magnitude of staff workload in RCH clinics. The study was conducted in 60 health facilities identified from five regions that had participated in the pilot phase of PMTCT implementation in the Mainland Tanzania. The average staff workload was calculated from staff-load obtained from attendance records and activity-time obtained by direct observation; and staff-time from records that were kept at the clinic. The average staff workload was found to be 50.5% (8-147%) for facilities providing PMTCT of HIV infection and 37.8% (11-82%) for facilities without PMTCT services. The average staff workload was computed on the assumption that all clients attending various antenatal clinics received PMTCT services from trained staff only and the result revealed staff workload of 87.2%. This study concludes that services for PMTCT of HIV infection can easily be scaled-up and integrated into RCH services using the already existing staff. In the wake of the human resource crisis in the health sector in developing countries, strategies to address the problem will need to go beyond numbers to address issues of staff productivity and their distribution.\n Copyright 2008 John Wiley & Sons, Ltd.", "Antenatal clinics are a key entry point into HIV treatment and care, together with interventions to reduce mother-to-child transmission (MTCT). Further evaluation is needed of interventions linking antenatal with antiretroviral (ARV) treatment services and effectiveness of triple-ARV regimens for reducing MTCT in resource-constrained settings.\n Data were gathered from HIV-infected women attending antenatal care from June 2004 to July 2005 at Coronation Women and Children Hospital, South Africa. After a patient record review, interventions were implemented to strengthen service linkages and integrate ARV treatment within antenatal care. Laboratory investigations were streamlined, including CD4 cell count testing at the first antenatal visit. MTCT risk for women initiating ARV treatment is compared with that of women-infant pairs receiving single-dose nevirapine (sd-NVP).\n In total, 164 pregnant women initiated ARV treatment and 863 received sd-NVP. After changes to service delivery, time-to-treatment initiation was reduced from a median of 56 days to 37 days (P = 0.041). The risk of MTCT for women receiving ARV treatment (5 [4.3%] of 116 women) was lower than for those given sd-NVP (74 [10.7%] of 692 women; P = 0.032).\n Strengthening linkages and integrating key components of ARV treatment within antenatal care reduces time-to-treatment initiation. In this setting, among women with a high MTCT risk, triple-ARV regimens are effective in reducing HIV infection in infants.", "The implementation of disease-specific research or service programs may have an ancillary beneficial or harmful impact on routine clinical services.\n We reviewed the records of 5801 first visits to 22 antenatal clinics from 1997 to 2004 in Lusaka, Zambia and examined documented syphilis rapid plasma reagin (RPR) screening and syphilis treatment before and after implementation of research and/or service programs in prevention of mother-to-child (PMTCT) HIV transmission.\n Compared with before PMTCT program implementation, the prevalence odds ratios (PORs) and 95% confidence intervals (CIs) for documented RPR screening were 0.9 (0.7 to 1.1) after implementation of research, 0.7 (0.6 to 0.8) after service, and 2.5 (2.1 to 3.0) after research and service programs.\n Documented RPR screening was improved after implementation of PMTCT research and service were operating simultaneously and not with research or service alone. Health policy makers and researchers should plan explicitly for how the targeted HIV programs, service, and/or research can have a broader primary care impact.", "Ukraine has the highest rate of HIV infection in Europe, with an estimated adult prevalence of 1.6 percent. The epidemic in Ukraine remains largely driven by injection drug use, and women of reproductive age are being increasingly affected. Prior research has highlighted the need to improve the quality of services for prevention of mother-to-child transmission (PMTCT) and to address other issues related to HIV counseling, testing, and care, especially in the context of antenatal and obstetric services.\n From 2004 to 2007, PATH led a collaborative effort to improve the quality of PMTCT services in Ukraine. Initial assessments included focus groups with Ukrainian women and review of existing educational materials. Interventions focused on training providers to improve skills in communication and referral to community-based support; they also addressed the underlying issue of stigma.\n Observational data demonstrated that providers who participated in the training intervention delivered PMTCT counseling of a consistently higher quality than did providers who did not undergo training. Exit interviews with clients confirmed these findings.\n An intervention focused on strengthening voluntary counseling and testing for HIV, forging partnerships with local organizations, and undoing HIV-related stigma can help to improve access to and quality of PMTCT services in antenatal care clinics.", "To measure changes in service utilization of a model integrating family planning with HIV counselling and testing (HCT), antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) in the Nigerian public health facilities.\n It is a retrospective survey of attendance and family planning commodity uptake in 71 health facilities in Nigeria that analyzes the preintegration and postintegration periods between March 2007 and January 2009.\n A prepost retrospective comparison of mean attendance at family planning clinics and couple-years of protection (CYP) compared 6 months preintegration with 9 months postintegration period. An analysis of service ratios was conducted, relating completed referrals at family planning clinics to service utilization at the referring HIV clinics.\n Mean attendance at family planning clinics increased significantly from 67.6 in preintegration to 87.0 in postintegration. The mean CYP increased significantly from 32.3 preintegration to 38.2 postintegration. Service ratio of referrals from each of the HIV clinics was low but increased in the postintegration period by 4, 34 and 42 per 1000 clients from HCT, ART and PMTCT clinics, respectively. Service ratios were higher in primary healthcare settings than in secondary or tertiary hospitals. Attendance by men at family planning clinics was significantly higher among clients referred from HIV clinics.\n Family planning-HIV integration using the referral model improved family planning service utilization by clients accessing HIV services, but further improvement is possible. Male utilization of family planning services also improved. The government of Nigeria should review the family planning user fee policy and scale up the integration in primary healthcare facilities.", "Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.\n The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged > or = 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%-4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%-9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%-7.0%) at age week 4 wk and 11.7% (95% CI 7.5%-15.9%) at 12 mo.\n This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.", "Pregnancy outcomes in women receiving highly active antiretroviral treatment (HAART) in Africa are not well described.\n HIV-1-infected pregnant women in the ANRS Ditrame Plus and the MTCT-Plus projects were included. Between March 2001 and July 2003, when HAART was not yet available, women eligible for HAART received a short-course antiretroviral regimen, zidovudine (ZDV) or (ZDV + lamivudine) and single dose of nevirapine for preventing mother-to-child transmission (PMTCT group). Between August 2003 and August 2007, eligible women for HAART received it (HAART group). The frequencies of low birth weight (LBW) (<2500 g), stillbirth and infant mortality are reported. Risk factors associated with LBW were investigated using a logistic regression model.\n Of the 326 HIV-infected pregnant women, 175 women received short-course antiretroviral (median CD4 cell count 177 cells/microl) and 151 received HAART (median CD4 cell count 182 cells/microl). At 12 months, three paediatric infections (2.3%) occurred in the HAART group vs. 25 (16.1%) in the PMTCT group (P < 0.001). The rate of LBW was 22.3% in the HAART group and 12.4% in the PMTCT group (P = 0.02). In multivariable analysis (n = 309), after adjustment on maternal CD4 cell count, WHO stage, age and maternal BMI, HAART initiated before pregnancy [adjusted odds ratio (OR) 2.88, 95% confidence interval (CI) 1.10-7.51] and during pregnancy (adjusted OR 2.12, 95% CI 1.15-4.65) and maternal BMI at delivery (adjusted OR 2.43, 95% CI 1.20-4.91) were associated with LBW.\n HAART in pregnant African women with advanced HIV disease substantially reduced mother-to-child transmission, but was associated with LBW." ]

[ "16708003", "12694632", "15466769", "16569189", "19775439", "17034605", "12817353", "17010115", "12358871" ]

[ "Cluster randomized controlled trial of the effectiveness of audit and feedback and educational outreach on improving nursing practice and patient outcomes.", "Randomised controlled trial of a theoretically grounded tailored intervention to diffuse evidence-based public health practice [ISRCTN23257060].", "A multimethod quality improvement intervention to improve preventive cardiovascular care: a cluster randomized trial.", "Use of an 'evidence-based implementation' strategy to implement evidence-based care of asthma into rural district hospital emergency departments.", "A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies.", "A randomized controlled trial of the effectiveness of pelvic floor therapies for urodynamic stress and mixed incontinence.", "Modifying dyspepsia management in primary care: a cluster randomised controlled trial of educational outreach compared with passive guideline dissemination.", "Cluster randomised trial of an active, multifaceted educational intervention based on the WHO Reproductive Health Library to improve obstetric practices.", "Multifaceted support to improve clinical decision making in diabetes care: a randomized controlled trial in general practice." ]

[ "Current understanding of implementation methods is limited, and research has focused on changing doctors' behaviors.\n Our aim was to evaluate the impact of audit and feedback and educational outreach in improving nursing practice and patient outcomes.\n Using a factorial design, cluster randomized controlled trial, we evaluated 194 community nurses in 157 family practices and 1078 patients with diagnosis of urinary incontinence (UI) for nurses compliance with evidence-linked review criteria for the assessment and management of UI and impact on psychologic and social well-being and symptoms. In the outreach arms, nurses' self-reported barriers informed development of tailored strategies.\n In comparison with educational materials alone, the implementation methods tested did not improve care at 6 months follow-up. Moderate rates of improvement (10-17% of patients) in performance for the assessment of UI and greater rates of improvement (20-30% of patients) for the management of care were found but effects were similar across arms. Improvement in patient outcomes was more consistently positive for educational outreach than for audit and feedback but differences were not significant. Adjustment for caseload size, severity or duration of UI and patients' age did not alter results.\n Printed educational materials alone may be as effective as audit and feedback and educational outreach in improving nurses' performance and outcomes of care for people with UI. Greater understanding of the underlying processes in improving performance within multidisciplinary teams through further, theory-driven studies with \"no intervention\" control groups and longer follow-up are needed.", "Previous studies have shown that Norwegian public health physicians do not systematically and explicitly use scientific evidence in their practice. They work in an environment that does not encourage the integration of this information in decision-making. In this study we investigate whether a theoretically grounded tailored intervention to diffuse evidence-based public health practice increases the physicians' use of research information.\n 148 self-selected public health physicians were randomised to an intervention group (n = 73) and a control group (n = 75). The intervention group received a multifaceted intervention while the control group received a letter declaring that they had access to library services. Baseline assessments before the intervention and post-testing immediately at the end of a 1.5-year intervention period were conducted. The intervention was theoretically based and consisted of a workshop in evidence-based public health, a newsletter, access to a specially designed information service, to relevant databases, and to an electronic discussion list. The main outcome measure was behaviour as measured by the use of research in different documents.\n The intervention did not demonstrate any evidence of effects on the objective behaviour outcomes. We found, however, a statistical significant difference between the two groups for both knowledge scores: Mean difference of 0.4 (95% CI: 0.2-0.6) in the score for knowledge about EBM-resources and mean difference of 0.2 (95% CI: 0.0-0.3) in the score for conceptual knowledge of importance for critical appraisal. There were no statistical significant differences in attitude-, self-efficacy-, decision-to-adopt- or job-satisfaction scales. There were no significant differences in Cochrane library searching after controlling for baseline values and characteristics.\n Though demonstrating effect on knowledge the study failed to provide support for the hypothesis that a theory-based multifaceted intervention targeted at identified barriers will change professional behaviour.", "Research is needed to validate effective and practical strategies for improving the provision of evidence-based medicine in primary care.\n To determine whether a multimethod quality improvement intervention was more effective than a less intensive intervention for improving adherence to 21 quality indicators for primary and secondary prevention of cardiovascular disease and stroke.\n 2-year randomized, controlled clinical trial with the practice as the unit of randomization.\n 20 community-based family or general internal medicine practices in 14 states. All used the same electronic medical record.\n 44 physicians, 17 midlevel providers, and approximately 200 staff members; data from the electronic medical records of 87,291 patients.\n All practices received copies of practice guidelines and quarterly performance reports. Intervention practices also hosted quarterly site visits to help them adopt quality improvement approaches and participated in 2 network meetings to share \"best practice\" approaches.\n The percentage of indicators at or above predefined targets and the percentage of patients who had achieved each clinical indicator.\n Intervention practices improved 22.4 percentage points (from 11.3% to 33.7%) in the percentage of indicators at or above the target; control practices improved 16.4 percentage points (from 6.3% to 22.7%). The 6.0-percentage point absolute difference between the intervention and control group was not statistically significant (P > 0.2). Patients in intervention practices had greater improvements than those in control practices for diagnoses of hypertension (improvement difference, 15.7 percentage points [95% CI, 5.2 to 26.3 percentage points]) and blood pressure control in patients with hypertension (improvement difference, 8.0 percentage points [CI, 0.0 to 16.0 percentage points]).\n The study involved a small number of practices and lacked a pure control group.\n Primary care practices that use electronic medical records and receive regular performance reports can improve their adherence to clinical practice guidelines for cardiovascular disease and stroke prevention.", "To determine if an evidence-based implementation (EBI) could lead to the successful implementation of evidence based care for adult asthma in small rural district hospitals.\n A controlled trial involving eight small rural hospitals (four each in the study and control groups) was conducted. Retrospective pre-intervention audits were conducted at all eight hospitals for 7 months (1 January 2004 to 31 July 2004) and evidence-practice gaps identified. An EBI was then used to implement established guidelines for the management of asthma in the study hospitals. Post-intervention audits were then performed over a period of 7 months (1 October 2004 to 31 April 2005).\n There were 52 presentations of asthma in the study hospitals in the pre-implementation phase and 47 post-implementation. The corresponding numbers for the control hospitals were 46 and 42 respectively. There were no statistically significant differences in the severity between the groups. Following the EBI there were significant improvements at the study hospitals for the documentation of severity (8% to 62%, p <0.001), use of spirometry (12% to 62%, p <0.001) and the use of written short-term asthma plans (9% to 26%, p = 0.05). There was a decrease in use of ipratropium in mild asthma (44% to 30%, p = 0.228), an increase in the use of systemic steroids (61% to 72%, p = 0.255) and no change in prescribing antibiotics for afebrile patients with asthma (21% to 21% p = 0.956). There was no significant change in practice at the control hospitals except for a decrease in the use of systemic steroids (48% to 21%, p = 0.011). For the six clinical indicators aggregate there was a significant increase in compliance with guidelines at the study hospitals (36% to 62%, p < 0.001) but no change at the control hospitals (31% to 31%, p = 0.970).\n The pre-intervention audits demonstrated low levels of compliance with asthma guidelines across six clinical indicators. An EBI significantly improved compliance across these six indicators, and no improvement was noted in the control hospitals. This study demonstrates that an EBI can alter clinical practice in small rural district hospitals.", "Significant resources and time are invested in the production of research knowledge. The primary objective of this randomized controlled trial was to evaluate the effectiveness of three knowledge translation and exchange strategies in the incorporation of research evidence into public health policies and programs.\n This trial was conducted with a national sample of public health departments in Canada from 2004 to 2006. The three interventions, implemented over one year in 2005, included access to an online registry of research evidence; tailored messaging; and a knowledge broker. The primary outcome assessed the extent to which research evidence was used in a recent program decision, and the secondary outcome measured the change in the sum of evidence-informed healthy body weight promotion policies or programs being delivered at health departments. Mixed-effects models were used to test the hypotheses.\n One hundred and eight of 141 (77%) health departments participated in this study. No significant effect of the intervention was observed for primary outcome (p < 0.45). However, for public health policies and programs (HPPs), a significant effect of the intervention was observed only for tailored, targeted messages (p < 0.01). The treatment effect was moderated by organizational research culture (e.g., value placed on research evidence in decision making).\n The results of this study suggest that under certain conditions tailored, targeted messages are more effective than knowledge brokering and access to an online registry of research evidence. Greater emphasis on the identification of organizational factors is needed in order to implement strategies that best meet the needs of individual organizations.\n The trial registration number and title are as follows: ISRCTN35240937 -- Is a knowledge broker more effective than other strategies in promoting evidence-based physical activity and healthy body weight programming?", "To assess the efficacy and cost-effectiveness of pelvic floor muscle therapies (PFMT) in women aged > or = 40 years with urodynamic stress incontinence (USI) and mixed UI.\n In a three-arm randomized controlled trial in Leicestershire and Rutland UK, 238 community-dwelling women aged > or = 40 years with USI in whom previous primary behavioural intervention had failed were randomized to receive either intensive PFMT (79), vaginal cone therapy (80) or to continue with primary behavioural intervention (79) for 3 months. The main outcome measure was the frequency of primary UI episodes, and secondary measures were pad-test urine loss, patient perception of problem, assessment of PF function, voiding frequency, and pad usage. Validated scales for urinary dysfunction, and impact on quality of life and satisfaction were collected at an independent interview.\n All three groups had a moderate reduction in UI episodes after intervention but there was no statistically significant difference among the groups. There were marginal improvements in voiding frequency for all groups, with no statistically significant difference among them.\n In women who have already had simple behavioural therapies (including advice on PFM exercises) for urinary dysfunction, the continuation of these behavioural therapies can lead to further improvement. The addition of vaginal cone therapy or intensive PFMT does not seem to contribute to further improvement. The improvement in pelvic floor function was significantly greater in the PFMT arm than in the control arm although this did not translate into changes in urinary symptoms.", "Quality improvement initiatives in health services rely upon the effective introduction of clinical practice guidelines. However, even well constructed guidelines have little effect unless supported by dissemination and implementation strategies.\n To test the effectiveness of 'educational outreach' as a strategy for facilitating the uptake of dyspepsia management guidelines in primary care.\n A pragmatic, cluster-randomised controlled trial of guideline introduction, comparing educational outreach with postal guideline dissemination alone.\n One-hundred and fourteen general practices (233 general practitioners) in the Salford and Trafford Health authority catchment area in the northwest of England.\n All practices received guidelines by post in July 1997. The intervention group practices began to receive educational outreach three months later. This consisted of practice-based seminars with hospital specialists at which guideline recommendations were appraised, and implementation plans formulated. Seminars were followed up with 'reinforcement' visits after a further 12 weeks. Outcome measures were: (a) the appropriateness of referral for; and (b) findings at, open access upper gastrointestinal endoscopy; (c) costs of GP prescriptions for acid-suppressing drugs, and (d) the use of laboratory-based serological tests for Helicobacter pylori. Data were collected for seven months before and/or after the intervention and analysed by intention-to-treat.\n (a) The proportion of appropriate referrals was higher in the intervention group in the six-month post-intervention period (practice medians: control = 50.0%, intervention = 63.9%, P < 0.05); (b) the proportion of major findings at endoscopy did not alter significantly; (c) there was a greater rise in overall expenditure on acid-suppressing drugs in the intervention as compared with the control group (+8% versus +2%, P = 0.005); and (d) the median testing rate per practice for H pylori in the post-intervention period was significantly greater in the intervention group (four versus O, P < 0.001).\n This study suggests that educational outreach may be more effective than passive guideline dissemination in changing clinical behaviour. It also demonstrates that unpredictable and unanticipated outcomes may emerge.", "We conducted a trial to evaluate the effect of an active, multifaceted educational strategy to promote the use of the WHO Reproductive Health Library (RHL) on obstetric practices.\n Cluster randomised trial. The trial was assigned the International Standardised Randomised Controlled Trial Number ISRCTN14055385.\n Twenty-two hospitals in Mexico City and 18 in the Northeast region of Thailand.\n The intervention consisted primarily of three interactive workshops using RHL over a period of 6 months. The focus of the workshops was to provide access to knowledge and enable its use. A computer and support for using both the computer and RHL were provided at each hospital. The control hospitals did not receive any intervention.\n The main outcome measures were changes in ten selected clinical practices as recommended in RHL starting approximately four to six months after the third workshop. Clinical practice data were collected at each hospital from 1000 consecutively delivered women or for a 6-month period whichever was reached sooner.\n The active, multifaceted educational intervention we employed did not affect the ten targeted practices in a consistent and substantive way. Iron/folate supplementation, uterotonic use after birth and breastfeeding on demand were already frequently practiced, and we were unable to measure external cephalic version. Of the remaining six practices, selective, as opposed to routine episiotomy policy increased in the intervention group (difference in adjusted mean rate = 5.3%; 95% CI -0.1 to 10.7%) in Thailand, and there was a trend towards an increased use of antibiotics at caesarean section in Mexico (difference in adjusted mean rate = 19.0%; 95% CI: -8.0 to 46.0%). There were no differences in the use of labour companionship, magnesium sulphate use for eclampsia, corticosteroids for women delivering before 34 weeks and vacuum extraction. RHL awareness (24.8-65.5% in Mexico and 33.9-83.3% in Thailand) and use (4.8-34.9% in Mexico and 15.5-76.4% in Thailand) increased substantially after the intervention in both countries.\n The multifaceted, active strategy to provide health workers with the knowledge and skills to use RHL to improve their practice led to increased access to and use of RHL, however, no consistent or substantive changes in clinical practices were detected within 4-6 months after the third workshop.", "To evaluate the effectiveness of a multifaceted intervention to improve the clinical decision making of general practitioners (GPs) for patients with diabetes. To identify practice characteristics which predict success.\n Cluster randomized controlled trial with 124 practices and 185 GPs in The Netherlands. The intervention group received feedback reports and support from a facilitator; the control group received no special attention. Outcome measures were the compliance rates with evidence-based recommendations pertaining to discussion of body weight control, discussion of problems with medication, blood pressure measurement, foot examination, eye examination, initiating anti-diabetic medication or increasing the dosage in cases of uncontrolled blood glucose, and scheduling a follow-up appointment.\n The GPs reported on their clinical decision making in 1410 consultations with Type 2 diabetic patients at baseline and 1449 consultations after the intervention period. The intervention resulted in statistically significant improvement for two of the seven outcome measures: foot examination (odds ratio 1.68; 95% confidence interval 1.19-2.39) and eye examination (1.52; 1.07-2.16). Discussion of problems with medication showed a near significant trend towards increased benefit for the intervention group (1.52; 0.99-2.32). Practice characteristics were not found to be related to the success of the intervention.\n Feedback reports with support from facilitators appear to increase rates of foot examination and eye examination in general practice. Alternative interventions should be explored to improve the pursuit of metabolic control by GPs." ]

[ "8602477", "2148221", "17268258", "19685848", "17621203", "15131431", "18564952", "15319761", "15507794" ]

[ "Physical performance, pain, pain behavior and subjective disability in patients with subacute low back pain.", "A controlled study on the outcome of inpatient and outpatient treatment of low back pain. Part III. Long-term follow-up of pain, disability, and compliance.", "Multidisciplinary rehabilitation for subacute low back pain: graded activity or workplace intervention or both? A randomized controlled trial.", "Comparison of short-term response to two spinal manipulation techniques for patients with low back pain in a military beneficiary population.", "Active exercise, education, and cognitive behavioral therapy for persistent disabling low back pain: a randomized controlled trial.", "Mini-intervention for subacute low back pain: two-year follow-up and modifiers of effectiveness.", "A comparison between chiropractic management and pain clinic management for chronic low-back pain in a national health service outpatient clinic.", "A randomized clinical trial comparing chiropractic adjustments to muscle relaxants for subacute low back pain.", "Early intervention for the management of acute low back pain: a single-blind randomized controlled trial of biopsychosocial education, manual therapy, and exercise." ]

[ "The aim of this paper was to study the physical performance, pain, pain behavior and disability in patients with subacute low back pain (LBP). The patients were blue-collar workers and had been sick-listed for 8 weeks due to subacute low back pain. A total of 103 patients were randomized, 51 of them to the intervention group and the other to a control group. Recordings of physical performance and complaints of LBP were done before and after treatment in the intervention group. The proportion of patients with no complaints of LBP was significantly greater in the intervention group than in the control group at the one-year follow-up. The patients who intra-individually improved their physical performance also intra-individually decreased their complaints of LBP. The intra-individual improvements were suggested to be important for the individual return to work.", "The long-term outcome results of inpatient and outpatient treatment of low back pain (LBP) were studied in 476 subjects (aged 35-54, 63% men) randomly assigned to three study groups: inpatients (n = 157), outpatients (n = 159), and controls (n = 160). The study included changes in the severity of low back pain, grade and disability, compliance with self-care, data on disability pensions, and days of sickness allowance during a 2.5-year follow-up period. These variables were used as outcome criteria. Pain and disability had decreased significantly in the two treated groups up to the 3-month follow-up. LBP was still a little slighter in the inpatients at the 1.5-year and 22-month follow-ups, but there were no significant differences between the groups in disability caused by LBP. The refresher programme carried out 1.5 years after the first one did not bring about as clear short-term improvement in pain and disability as the first treatment. During the whole 2.5-year follow-up compliance with self-care was better in the two treated groups, especially in the inpatients. Days of sickness allowance had increased somewhat more in the controls than in the inpatients during the follow-up. No differences between the groups were found in the number of disability pensions granted.", "Population-based randomized controlled trial.\n To assess the effectiveness of workplace intervention and graded activity, separately and combined, for multidisciplinary rehabilitation of low back pain (LBP).\n Effective components for multidisciplinary rehabilitation of LBP are not yet established.\n Participants sick-listed 2 to 6 weeks due to nonspecific LBP were randomized to workplace intervention (n = 96) or usual care (n = 100). Workplace intervention consisted of workplace assessment, work modifications, and case management involving all stakeholders. Participants still sick-listed at 8 weeks were randomized for graded activity (n = 55) or usual care (n = 57). Graded activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles. Outcomes were lasting return to work, pain intensity and functional status, assessed at baseline, and at 12, 26, and 52 weeks after the start of sick leave.\n Time until return to work for workers with workplace intervention was 77 versus 104 days (median) for workers without this intervention (P = 0.02). Workplace intervention was effective on return to work (hazard ratio = 1.7; 95% CI, 1.2-2.3; P = 0.002). Graded activity had a negative effect on return to work (hazard ratio = 0.4; 95% CI, 0.3-0.6; P < 0.001) and functional status. Combined intervention had no effect.\n Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP. Graded activity or combined intervention is not advised.", "To determine whether military health care beneficiaries with low back pain (LBP) who are likely to respond successfully to spinal manipulation experience a difference in short-term clinical outcomes based on the manipulation technique that is used.\n Sixty patients with LBP identified as likely responders to manipulation underwent a standardized clinical examination and were randomized to receive a lumbopelvic (LP) or lumbar neutral gap (NG) manipulation technique. Outcome measures were a numeric pain rating scale and the modified Oswestry Disability Questionnaire.\n Both the LP and NG groups experienced statistically significant reductions in pain and disability at 48 hours postmanipulation. The improvements seen in each group were small because of the short follow-up. There were no statistically significant or clinically meaningful differences in pain or disability between the two groups.\n The two manipulation techniques used in this study were equally effective at reducing pain and disability when compared at 48 hours posttreatment. Clinicians may employ either technique for the treatment of LBP and can expect similar outcomes in those who satisfy the clinical prediction rule (CPR). Further research is required to determine whether differences exist at longer-term follow-up periods, after multiple treatment sessions, or in different clinical populations.", "A randomized controlled trial.\n To determine 1) whether, among patients with persistent disabling low back pain (LBP), a group program of exercise and education using a cognitive behavioral therapy (CBT) approach, reduces pain and disability over a subsequent 12-month period; 2) the cost-effectiveness of the intervention; and 3) whether a priori preference for type of treatment influences outcome.\n There is evidence that both exercise and CBT delivered in specialist settings is effective in improving LBP. There is a lack of evidence on whether such interventions, delivered by trained individuals in primary care, result in improved outcomes.\n The study was conducted in nine family medical practices in East Cheshire, UK. Patients 18 to 65 years of age, consulting with LBP, were recruited; those still reporting LBP 3 months after the initial consultation were randomized between the two trial arms. The intervention arm received a program of eight 2-hour group exercise session over 6 weeks comprising active exercise and education delivered by physiotherapists using a CBT approach. Both arms received an educational booklet and audio-cassette. The primary outcome measures were pain (0-100 Visual Analogue Scale) and disability (Roland and Morris Disability Scale; score 0-24).\n A total of 196 subjects (84%) completed follow-up 12 months after the completion of the intervention program. The intervention showed only a small and nonsignificant effect at reducing pain (-3.6 mm; 95% confidence interval, -8.5, 1.2 mm) and disability (-0.6 score; 95% confidence interval, -1.6, 0.4). The cost of the intervention was low with an incremental cost-effectiveness ratio of pound5000 (U.S. $8650) per quality adjusted life year. In addition, patients allocated to the intervention that had expressed a preference for it had clinically important reductions in pain and disability.\n This intervention program produces only modest effects in reducing LBP and disability over a 1-year period. The observation that patient preference for treatment influences outcome warrants further investigation.", "Randomized controlled trial.\n To Investigate the long-term effectiveness, costs, and effect modifiers of a mini-intervention, provided in addition to the usual care, and the incremental effect of a worksite visit for patients with subacute disabling low back pain (LBP).\n A mini-intervention was earlier proved to be an effective treatment for subacute LBP. Whether the beneficial effect is sustained is not known. Furthermore, modifiers of a treatment effect are largely unknown.\n A total of 164 patients with subacute LBP randomized into a mini-intervention (A, n = 56), a mini-intervention plus a worksite visit (B, n = 51), or the usual care (C, n = 57). Mini-intervention consisted of a detailed assessment of the patients' history, beliefs, and physical findings by a physician and a physiotherapist, followed by recommendations and advice. The usual care patients received the conventional care. Pain, disability, health-related quality of life, satisfaction with care, days on sick leave, and health care consumption and costs were measured during a 24-month follow-up. Thirteen candidate modifiers were tested for each outcome.\n There were no differences between the three treatment arms regarding the intensity of pain, the perceived disability, or the health-related quality of life. However, mini-intervention decreased occurrence of daily (A vs., C, P = 0.01) and bothersome (A vs. C, P < 0.05) pain and increased treatment satisfaction. Costs resulting from LBP were lower in the intervention groups (A 4670 Euros, B 5990 Euros) than in C (C 9510 Euros) (A vs. C, P = 0.04; and B vs. C, not significant). The average number of days on sick leave was 30 in A, 45 in B, and 62 in C (A vs. C, P = 0.03; B vs. C, not significant). The perceived risk for not recovering was the strongest modifier of treatment effect. Mental and mental-physical workers in A and B were less often on sick leave than those in C.\n Mini-intervention is an effective treatment for subacute LBP. Despite lack of a significant effect on intensity of low back pain and perceived disability, mini-intervention, including proper recommendations and advice, according to the \"active approach,\" is able to reduce LBP-related costs. The perceived risk of not recovering was the strongest modifier of treatment effect. In alleviating pain, the intervention was most effective among the patients with a high perceived risk of not recovering.", "To compare outcomes in perception of pain and disability for a group of patients suffering with chronic low-back pain (CLBP) when managed in a hospital by either a regional pain clinic or a chiropractor.\n The study was a pragmatic, randomized, controlled trial.\n The trial was performed at a National Health Service (NHS) hospital outpatient clinic (pain clinic) in the United Kingdom.\n Patients with CLBP (i.e., symptom duration of >12 weeks) referred to a regional pain clinic (outpatient hospital clinic) were assessed and randomized to either chiropractic or pain-clinic management for a period of 8 weeks. The study was pragmatic, allowing for normal treatment protocols to be used. Treatment was administered in an NHS hospital setting.\n The Roland-Morris Disability Questionnaire (RMDQ) and Numerical Rating Scale were used to assess changes in perceived disability and pain. Mean values at weeks 0, 2, 4, 6, and 8 were calculated. The mean differences between week 0 and week 8 were compared across the two treatment groups using Student's t-tests. Ninety-five percent (95%) confidence intervals (CIs) for the differences between groups were calculated.\n Randomization placed 12 patients in the pain clinic and 18 in the chiropractic group, of which 11 and 16, respectively, completed the trial. At 8 weeks, the mean improvement in RMDQ was 5.5 points greater for the chiropractic group (decrease in disability by 5.9) than for the pain-clinic group (0.36) (95% CI 2.0 points to 9.0 points; p = 0.004). Reduction in mean pain intensity at week 8 was 1.8 points greater for the chiropractic group than for the pain-clinic group (p = 0.023). Conclusions: This study suggests that chiropractic management administered in an NHS setting may be effective for reducing levels of disability and perceived pain during the period of treatment for a subpopulation of patients with CLBP.", "The adult lifetime incidence for low back pain is 75% to 85% in the United States. Investigating appropriate care has proven difficult, since, in general, acute pain subsides spontaneously and chronic pain is resistant to intervention. Subacute back pain has been rarely studied.\n To compare the relative efficacy of chiropractic adjustments with muscle relaxants and placebo/sham for subacute low back pain.\n A randomized, double-blind clinical trial.\n Subjects (N = 192) experiencing low back pain of 2 to 6 weeks' duration were randomly allocated to 3 groups with interventions applied over 2 weeks. Interventions were either chiropractic adjustments with placebo medicine, muscle relaxants with sham adjustments, or placebo medicine with sham adjustments. Visual Analog Scale for Pain, Oswestry Disability Questionnaire, and Modified Zung Depression Scale were assessed at baseline, 2 weeks, and 4 weeks. Schober's flexibility test, acetaminophen usage, and Global Impression of Severity Scale (GIS), a physician's clinical impression used as a secondary outcome, were assessed at baseline and 2 weeks.\n Baseline values, except GIS, were similar for all groups. When all subjects completing the protocol were combined (N = 146), the data revealed pain, disability, depression, and GIS decreased significantly (P <.0001); lumbar flexibility did not change. Statistical differences across groups were seen for pain, a primary outcome, (chiropractic group improved more than control group) and GIS (chiropractic group improved more than other groups). No significant differences were seen for disability, depression, flexibility, or acetaminophen usage across groups.\n Chiropractic was more beneficial than placebo in reducing pain and more beneficial than either placebo or muscle relaxants in reducing GIS.", "A single blind randomized controlled trial comparing two models of care for patients with acute simple low back pain.\n To compare two research-based models of care for acute low back pain and investigate the effect of the timing of physical intervention.\n National guidelines offer conflicting information on the delivery of physical treatment in the management of acute low back pain. The guidelines suggest two different models of care. Direct comparisons between these models are lacking in the literature. The present study aims to compare these approaches to the management of acute low back pain.\n Among 804 referred patients, 102 subjects met the specific admission criteria and were randomly assigned to an \"assess/advise/treat\" group or an \"assess/advise/wait\" group. The intervention consisted of biopsychosocial education, manual therapy, and exercise. Assessment of short-term outcome enables comparison to be made between intervention and advice to stay active. Assessment of long-term outcome enables comparison to be made between early and late intervention. Study outcomes of reported pain (Visual Analogue Scale), functional disability (the Roland and Morris Disability Questionnaire), mood (Modified Zung Self Rated Depression Score, Modified Somatic Perception Questionnaire, State-Trait Anxiety Inventory), general health (Euroqol), and quality of life (Short Form 36) were assessed at baseline, 6 weeks, 3 months, and 6 months.\n At 6 weeks, the assess/advise/treat group demonstrated greater improvements in disability, mood, general health, and quality of life than patients in the assess/advise/wait group (P < 0.05). Disability and pain were not significantly different between the groups at long-term follow up (P > 0.05). However, mood, general health, and quality of life remained significantly better in the assess/advise/treat group (P < 0.05).\n At short-term, intervention is more effective than advice on staying active, leading to more rapid improvement in function, mood, quality of life, and general health. The timing of intervention affects the development of psychosocial features. If treatment is provided later, the same psychosocial benefits are not achieved. Therefore, an assess/advise/treat model of care seems to offer better outcomes than an assess/advise/wait model of care." ]

[ "10419922", "10535881", "15057894", "770224", "16250039", "3481038", "3533699", "9252088", "2184355" ]

[ "Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial.", "A prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis.", "A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results.", "A prospective controlled trial of azathioprine in primary biliary cirrhosis.", "Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis.", "Transient acute hepatotoxicity of high-dose methotrexate therapy during childhood.", "Randomized trial of chlorambucil for primary biliary cirrhosis.", "The combination of ursodeoxycholic acid and methotrexate for primary biliary cirrhosis is not better than ursodeoxycholic acid alone.", "A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis." ]

[ "New treatments for primary biliary cirrhosis (PBC) need to be evaluated. We conducted a single-center double-blind, randomized trial of methotrexate, 7.5 mg/wk (n = 30), vs. placebo (n = 30) for up to 6 years in PBC.\n Methods included three monthly symptom assessment and liver function tests and liver biopsy and gastroscopy at baseline, after 2 years, and after 4-6 years.\n Patients randomized to methotrexate had, compared with patients randomized to placebo, (1) significantly lower on-treatment serum alkaline phosphatase, gamma-glutamyltransferase, immunoglobulin (Ig) M, IgG, and (after 24 months) aspartate aminotransferase and alanine aminotransferase levels (P < 0.02-0.001 by analysis of covariance to adjust for baseline differences); (2) a nonsignificant trend toward lower on-treatment pruritus scores; (3) similar on-treatment Knodell inflammatory scores but nonsignificant trends toward lower Knodell fibrosis score and less ductopenia; (4) a trend toward greater increases in serum bilirubin level and Mayo score with time (both significant after 5 years of follow-up); and (5) a 2.9-fold (95% confidence interval, 0.85-10.25-fold) increase the rate of death or liver transplantation as a result of liver disease during or after the trial (P = 0.09) in a Cox multivariate regression analysis compared with patients randomized to placebo.\n These results do not support the clinical use of low-dose methotrexate in PBC.", "The aim of this study was to determine if colchicine or methotrexate improves blood test results, symptoms, and/or liver histology in patients with primary biliary cirrhosis.\n Patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase (ALP) levels were at least 2 times above normal and who were not yet candidates for liver transplantation received colchicine or methotrexate and were followed up for 2 years.\n In patients receiving colchicine (n = 43), mean pruritus score decreased from 1.63 to 1.12 (P = 0.04), ALP level from 494 to 355 U/L (P < 0.0001), and alanine aminotransferase (ALT) level from 79 to 61 U/L (P < 0.0001). In patients receiving methotrexate (n = 42), pruritus score decreased from 1.25 to 0.44 (P = 0.0001), ALP from 478 to 235 U/L (P < 0.0001), and ALT from 96 to 61 U/L (P = 0.0001). Methotrexate but not colchicine significantly improved liver histology (P = 0.005) and serum immunoglobulin G levels (P = 0.0002). Methotrexate improved most blood test results more than colchicine. Serum bilirubin levels increased slightly with each drug, and albumin levels decreased slightly.\n Both colchicine and methotrexate improved biochemical test results and symptoms in primary biliary cirrhosis, but the response to methotrexate was greater.", "Primary biliary cirrhosis frequently progresses despite treatment with ursodeoxycholic acid (UDCA), the only approved therapy. Previous studies suggested that colchicine and methotrexate may improve biochemical tests of liver function, symptoms, and liver histology. The aim of the present study was to determine if the addition of colchicine or methotrexate to UDCA would improve survival free of liver transplantation. Eighty-five patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase levels were at least twice the normal level and who were not yet candidates for liver transplantation were randomly assigned to receive colchicine or methotrexate in a double-blind study. UDCA was administered to all patients after 2 years. The primary end point was survival free of liver transplantation. Patients were followed up for a total of up to 10 years or until treatment failure. Data were analyzed on an intention-to-treat basis. Transplant-free survival was similar in both groups: 0.57 for colchicine plus UDCA and 0.44 for methotrexate plus UDCA, results that are similar to those predicted by the Mayo prognostic model. Significant improvement in liver biochemical tests and liver histology was observed in a subset of patients in both treatment groups who remained in the study for all 10 years. In conclusion, neither colchcine plus UDCA nor methotrexate plus UDCA improved survival beyond that predicted by the Mayo prognostic model. However, clinical, histologic, and biochemical improvement observed among those who remained in the study for 10 years suggests a possible benefit of these drugs in a subset of patients.", "Between 1968 and 1974, azathioprine has been used in a controlled prospective trial to treat patients with symptomatic but precirrhotic primary cirrhosis. Forty-five patients were admitted, of whom 22 were given azathioprine in a dose of 2 mg per kg of body weight. During the 1st year, serum aspartate transaminase levels showed a significant change in favor of the treated group, but improvement did not continue. Throughout the trial, serum alkaline phosphatase, bilirubin, cholesterol, albumin and immunoglobulin M values showed no significant change. Titers of serum mitochondrial antibodies tended to become negative more often in the treated than the untreated. Pruritus cannot be assessed objectively, but seemed less in the treated than in controls. Serial hepatic biopsy specimens showed the development of cirrhosis equally in the two groups. Survival, as judged by the life table method, was similar for the first 5 years of the trial. There was, however, a significant difference in favor of the treated group in the 6th year, although the number of patients available for assessment at that time was extremely small.", "This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.", "Serial liver-enzyme determinations were performed on 36 children with acute lymphoblastic leukemia who were randomized to receive either conventional intrathecal methotrexate (MTX) therapy with cranial irradiation, or an investigational high-dose MTX regimen consisting of 10 courses of 33,600 mg/m2 over 24 hours, with high-dose leucovorin rescue. Both groups of patients received intermittent low-dose oral MTX during maintenance therapy. Serum transaminase elevations in the group of conventionally treated patients were infrequent and moderate in severity (less than 300 IU/liter). In the investigational group, however, the majority of patients had severe, acute increases in SGPT (greater than 300 IU/liter), with peaks up to 1000 to 2000 IU/liter. The incidence and severity of acute transaminasemia were directly proportional to the number of high-dose MTX courses received: courses 1, 2, 3, 4, 5, and 6 caused transaminase elevations in 31%, 50%, 50%, 73%, 100%, and 100% of courses, respectively, and 0%, 14%, 20%, 44%, 55%, and 92%, respectively, were over 300 IU/liter. Patients in both treatment groups developed a pattern of increasing serum alkaline phosphatase concentrations after initiation of low-dose oral MTX therapy; isoenzyme analysis indicated that this effect was osseous rather than hepatic. Serum bilirubin was rarely elevated. Transaminases returned to normal within 1 to 2 weeks after each high-dose MTX treatment, and with follow-up for as long as 7 years, no patient has developed clinical evidence of residual liver disease, after 3 years of high-dose MTX therapy and multiple other antileukemia drugs. The acute hypertransaminasemia frequently observed after high-dose MTX therapy is transient and reversible, and, in children, does not appear to result in chronic liver disease.", "Twenty-four patients with primary biliary cirrhosis were entered into a prospective, randomized trial of chlorambucil therapy. Thirteen patients received chlorambucil (0.5-4 mg/day) and 11 patients received no therapy; all have been followed for 2-6 yr (mean, 4.1 yr). Two control but no treated patients died. Average serum bilirubin, serum aspartate aminotransferase activities, and albumin levels improved or remained unchanged in treated patients but worsened in controls. Serum alkaline phosphatase levels did not change in either group. Immunoglobulin M levels decreased and became normal in all treated patients but in only 3 control patients. Liver biopsy histology revealed an improvement in inflammatory cell infiltrate in treated patients in comparison with controls, but no significant change in degree of fibrosis or the histologic stage of disease. Side effects of therapy included bone marrow suppression necessitating discontinuation of the drug in 4 patients. These findings indicate that chlorambucil therapy may retard the progression of primary biliary cirrhosis. Whether such therapy will ultimately decrease morbidity and improve survival in this disease can only be demonstrated by large-scale, placebo-controlled trials.", "Many therapies have been tried in primary biliary cirrhosis. It has been suggested that a combination of ursodeoxycholic acid and methotrexate may offer advantages. Because the benefit and safety of this combination is uncertain, we conducted this prospective, randomized, double-blind, controlled trial.\n Twenty-five patients with well-defined primary biliary cirrhosis were randomly assigned to receive either ursodeoxycholic acid (500 mg/day) plus methotrexate (10 mg/week) or ursodeoxycholic acid plus placebo for a period of 48 weeks. Clinical, biochemical and histologic evolution were assessed.\n In both groups the clinical response was similar and heterogeneous. In patients of ursodeoxycholic acid alone group, biochemical and histologic changes were comparable to those of patients of ursodeoxycholic acid plus methotrexate at 48 weeks. The addition of methotrexate was not associated with substantial adverse affects.\n The use of methotrexate in combination with ursodeoxycholic acid was not followed by an additive benefit over ursodeoxycholic acid alone, nor was substantial toxicity added. Unless larger and longer controlled trials with clinical, biochemical and histologic controls show it to be a safe and effective therapy for primary biliary cirrhosis, ursodeoxycholic acid+methotrexate should not be used as a proven and accepted treatment.", "Primary biliary cirrhosis is a progressive disease of the liver characterized by the immunologic destruction of bile ducts; effective therapy is lacking. We therefore evaluated the safety and efficacy of low-dose cyclosporine in 29 patients with primary biliary cirrhosis without evidence of damage to the lobular architecture (precirrhotic disease) or portal hypertension. The patients were randomly assigned to receive either cyclosporine (4 mg per kilogram of body weight per day) or placebo. After one year 17 of the 19 patients assigned to cyclosporine had improvement or stability in their degree of fatigue, and 18 in their degree of pruritus. In contrast, among the 10 patients assigned to placebo, fatigue increased in 4 (P less than 0.06) and pruritus worsened in 6 (P less than 0.001). Those assigned to cyclosporine also had significant decreases in serum levels of bilirubin, alanine aminotransferase, alkaline phosphatase, gamma globulin, and the titer of antimitochondrial antibodies. For the 20 patients who have completed two years in the study, liver biopsies (coded specimens) showed evidence of histologic progression in only 1 of 13 patients in the cyclosporine group, as compared with 5 of 7 in the placebo group (P less than 0.003). No patient has permanently discontinued cyclosporine because of side effects; however, signs of nephrotoxicity developed in 12 of 19, and 9 of 19 had increased blood pressure. We conclude that in patients with precirrhotic primary biliary cirrhosis, immunosuppressive therapy with cyclosporine is promising and deserves further evaluation." ]

[ "9655655", "10098823", "15080865", "16672699", "10811511", "11075740", "17592075", "12618680", "8615305" ]

[ "Randomised comparison of percutaneous angioplasty vs continued medical therapy for hypertensive patients with atheromatous renal artery stenosis. Scottish and Newcastle Renal Artery Stenosis Collaborative Group.", "Behavioral effects of a comprehensive, multifactorial program for lifestyle change after percutaneous transluminal coronary angioplasty: a prospective, randomized controlled study.", "A multi-centre randomised controlled trial of minimally invasive direct coronary bypass grafting versus percutaneous transluminal coronary angioplasty with stenting for proximal stenosis of the left anterior descending coronary artery.", "Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery.", "Percutaneous transluminal angioplasty with or without stenting for femoropopliteal occlusions? A randomized controlled study.", "A prospective randomized trial comparing stenting to internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis: the SIMA trial. Stenting vs Internal Mammary Artery.", "Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST).", "Systematic versus selective stent placement after superficial femoral artery balloon angioplasty: a multicenter prospective randomized study.", "Rotational atherectomy with adjunctive balloon angioplasty versus conventional percutaneous transluminal coronary angioplasty in type B2 lesions: results of a randomized study." ]

[ "Data from randomised studies are lacking on the value of interventional procedures in the management of atheromatous renal artery stenosis. This randomised prospective trial compared the effects on blood pressure (BP) and renal function of percutaneous transluminal angioplasty vs medical therapy in hypertensive patients with both unilateral and bilateral disease.\n A total of 135 eligible patients were identified, of whom 55 (44%) were randomised. Eligible patients had sustained hypertension, with a minimum diastolic BP of 95 mm Hg on at least two anti-hypertensive drugs. Renal artery stenosis was defined by renal angiography as at least 50% stenosis in the affected vessel. All patients were observed during an initial 4-week run-in period on a fixed drug regimen and subsequent changes measured from this 4-week baseline.\n Blood pressure fell during the run-in period in all groups. In patients with bilateral renal artery stenosis randomised to angioplasty, a statistically significant (P<0.05) fall in BP was observed at latest follow-up (range 3-54 months). The mean fall in BP at latest follow-up in the angioplasty group, corrected for the medical group response, was 26/10 mm Hg. In patients with unilateral renal artery stenosis, no statistically significant or clinically important differences in outcome were observed between the two groups. No significant differences or trends in serum creatinine were observed between or within any group during follow-up. Major outcome events (death, myocardial infarction, heart failure, stroke, dialysis) were similar in the angioplasty and medical groups during follow-up. In the 40/135 patients undergoing angioplasty, serious or potentially serious complications attributable to the procedure were observed in 11 patients, bleeding at the arterial site (8 patients) being the most frequent.\n In hypertensive patients with atheromatous renal artery stenosis, percutaneous renal angioplasty results in a modest improvement in systolic BP compared with medical therapy alone. This benefit was confined to patients with bilateral disease. No patient was 'cured', renal function did not improve, and intervention was accompanied by a significant complication rate.", "A group of 93 coronary patients recently treated with percutaneous transluminal coronary angioplasty (PTCA) were randomly assigned to either an intervention or a control group. Subjects in the intervention group participated in a comprehensive behaviorally oriented program aimed at achieving significant long-term changes in risk factor-related lifestyle behavior. Assessments of lifestyle behaviors, psychological factors, biological risk factors, and rehabilitation as well as secondary prevention endpoints were carried out, at inclusion and after 12 months. Results showed that the intervention patients, as compared with controls, improved significantly on measures assessing smoking, exercise, and diet habits. These self-rated changes were confirmed by weight reductions and improved exercise capacity, as well as by between-group differences in subclinical chest pain during an exercise test. However, few effects were found on the different psychological variables, as well as on morbidity or return to work.", "To compare the clinical- and cost-effectiveness of minimally invasive direct coronary artery bypass grafting (MIDCAB) and percutaneous transluminal coronary angioplasty (PTCA) with or without stenting in patients with single-vessel disease of the left anterior descending coronary artery (LAD).\n Multi-centre randomised trial without blinding. The computer-generated sequence of randomised assignments was stratified by centre, allocated participants in blocks and was concealed using a centralised telephone facility.\n Four tertiary cardiothoracic surgery centres in England.\n Patients with ischaemic heart disease with at least 50% proximal stenosis of the LAD, suitable for either PTCA or MIDCAB, and with no significant disease in another vessel.\n Patients randomised to PTCA had local anaesthetic and underwent PTCA according to the method preferred by the operator carrying out the procedure. Patients randomised to MIDCAB had general anaesthetic. The chest was opened through an 8-10-cm left anterior thoracotomy. The ribs were retracted and the left internal thoracic artery (LITA) harvested. The pericardium was opened in the line of the LAD to confirm the feasibility of operation. The distal LITA was anastomosed end-to-side to an arteriotomy in the LAD. All operators were experienced in carrying out MIDCAB.\n The primary outcome measure was survival free from cardiac-related events. Relevant events were death, myocardial infarction, repeat coronary revascularisation and recurrence of symptomatic angina or clinical signs of ischaemia during an exercise tolerance test at annual follow-up. Secondary outcome measures were complications, functional outcome, disease-specific and generic quality of life, health and social services resource use and their costs.\n A total of 12,828 consecutive patients undergoing an angiogram were logged at participating centres from November 1999 to December 2001. Of the 1091 patients with proximal stenosis of the LAD, 127 were eligible and consented to take part; 100 were randomised and the remaining 27 consented to follow-up. All randomised participants were included in an intention-to-treat analysis of survival free from cardiac-related events, which found a non-significant benefit from MIDCAB. Cumulative hazard rates at 12 months were estimated to be 7.1 and 9.2% for MIDCAB and PTCA, respectively. There were no important differences between MIDCAB and PTCA with respect to angina symptoms or disease-specific or generic quality of life. The total NHS procedure costs were 1648 British pounds and 946 British pounds for MIDCAB and PTCA, respectively. The costs of resources used during 1 year of follow-up were 1033 British pounds and 843 British pounds, respectively.\n The study found no evidence that MIDCAB was more effective than PTCA. The procedure costs of MIDCAB were observed to be considerably higher than those of PTCA. Given these findings, it is unlikely that MIDCAB represents a cost-effective use of resources in the reference population. Recent advances in cardiac surgery mean that surgeons now tend to carry out off-pump bypass grafting via a sternotomy instead of MIDCAB. At the same time, cardiologists are treating more patients with multi-vessel disease by PTCA. Future primary research should focus on this comparison. Other small trials of PTCA versus MIDCAB have now finished and a more conclusive answer to the original objective could be provided by a systematic review.", "Because stent implantation for disease of the superficial femoral artery has been associated with high rates of late clinical failure, percutaneous transluminal angioplasty is preferred for endovascular treatment, and stenting is recommended only in the event of suboptimal technical results. We evaluated whether primary implantation of a self-expanding nitinol (nickel-titanium) stent yielded anatomical and clinical benefits superior to those afforded by percutaneous transluminal angioplasty with optional secondary stenting.\n We randomly assigned 104 patients who had severe claudication or chronic limb ischemia due to stenosis or occlusion of the superficial femoral artery to undergo primary stent implantation (51 patients) or angioplasty (53 patients). Restenosis and clinical outcomes were assessed at 6 and 12 months.\n The mean (+/-SD) length of the treated segment was 132+/-71 mm in the stent group and 127+/-55 mm in the angioplasty group. Secondary stenting was performed in 17 of 53 patients (32 percent) in the angioplasty group, in most cases because of a suboptimal result after angioplasty. At 6 months, the rate of restenosis on angiography was 24 percent in the stent group and 43 percent in the angioplasty group (P=0.05); at 12 months the rates on duplex ultrasonography were 37 percent and 63 percent, respectively (P=0.01). Patients in the stent group were able to walk significantly farther on a treadmill at 6 and 12 months than those in the angioplasty group.\n In the intermediate term, treatment of superficial-femoral-artery disease by primary implantation of a self-expanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting. (ClinicalTrials.gov number, NCT00281060.).\n Copyright 2006 Massachusetts Medical Society.", "To investigate the-one year outcome of PTA and stenting and PTA alone for femoropopliteal occlusions.\n Randomized prospective study\n 32 patients with femoropopliteal occlusions were randomized into two treatment groups: PTA and Strecker-stent (n=15) and PTA alone (n=17). The median age of the patients was 71 years. All patients had chronic limb ischaemia, 66% had tissue loss, 19% had rest pain and 15% had disabling claudication. The median ABPI was 0.45. The occlusion was confined to the superficial femoral artery in 30 cases and to the popliteal artery in 2 cases. The median length of the occlusions was 7.3 cm. Aspirin (ASA), 160 mg daily, was administrated postoperatively but no anticoagulation was used. The follow-up included: clinical examination, measurement of ABPI and control angiography at 12 months or earlier when necessary (20 patients).\n There was no mortality or limb loss as a consequence of the treatment. There were six (16%) immediate major complications in five patients. In the PTA group, one patient had a myocardial infarction and three patients needed arteriography due to bleeding. In the stent group, one patient required arteriography and embolectomy. The one-year mortality was 6% and there were no amputations. Four patients (two in each group) were operated on with a femorodistal bypass. The rate of clinical improvement was 71% after PTA and stent and 60% after PTA alone (p=0.17). An increased ABPI (>0.10) was shown in 50% of the stent group and 61% in the PTA group (p=0.17). Angiographic re-occlusions were seen in 33% and 75% in the stent and PTA groups respectively (p=0.17), while the rate of restenosis was significantly higher in the stent group (50% vs 25%) (p=0.033).\n Stenting following PTA for femoropopliteal occlusions does not significantly improve neither the clinical state nor the clinical/angiographic patency. The results do not justify any routine placement of stent following PTA in the successfully recanalized femoropopliteal arteries. The low rate of acceptance of a follow-up angiography indicates that this kind of study should preferably use duplex scanning instead of angiography for follow-up.", "To compare coronary artery bypass grafting (CABG) with percutaneous transluminal coronary angioplasty (PTCA) in patients with proximal, isolated de novo left anterior descending coronary artery disease and left ventricular ejection fraction of 45%.\n In the multicenter Stenting vs Internal Mammary Artery (SIMA) study, patients were randomly assigned to PTCA and stent implantation or to CABG (using the internal mammary artery). The primary clinical composite end point was event-free survival, including death, myocardial infarction, and the need for additional revascularization. Secondary end points were functional class, antianginal treatment, and quality of life. Analyses were by intention to treat.\n Of 123 patients who accepted randomization, 59 underwent CABG, and 62 were treated with stent implantation (2 patients were excluded because of protocol violation). At a mean +/- SD follow-up of 2.4+/-0.9 years, a primary end point had occurred in 19 patients (31%) in the stent group and in 4 (7%) in the CABG group (P<.001). This significant difference in clinical outcome is due to a higher incidence of additional revascularization in the stent group, the incidence of death and myocardial infarction being similar (7% vs 7%, respectively; P=.90). The functional class, need for antianginal drug, and quality-of-life assessment showed no significant differences.\n Both stent implantation and CABG are safe and highly effective treatments to relieve symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Both are associated with a low and comparable incidence of death and myocardial infarction. However, similar to PTCA alone, a percutaneous approach using elective stent placement remains hampered by a higher need for repeated intervention because of restenosis.", "Endoluminal treatment of superficial femoral artery lesions is a matter of controversy. The present study was designed to investigate the impact of nitinol stenting of superficial femoral artery lesions with a maximum length of 10 cm on restenosis and clinical outcomes at 1 year.\n Two hundred forty-four patients (168 men; 66+/-9 years) with a single superficial femoral artery lesion and chronic limb ischemia were randomized to implantation of a single Bard Luminexx 3 stent (123 patients) or stand-alone percutaneous transluminal angioplasty (PTA) (121 patients). Mean lesion length was 45 mm. Technical success (residual stenosis <50% for PTA, <30% for stenting) was achieved in 96 patients assigned to PTA (79%) and 117 patients assigned to stenting (95%); 13 PTA group patients (11%) \"crossed over\" to stenting. At 1 year, the primary end point of ultrasound-assessed binary restenosis was reached in 39 of 101 PTA group patients (38.6%) and 32 of 101 stent group patients (31.7%; absolute treatment difference, -6.9%; 95% CI, -19.7% to 6.2%; P=0.377). Target lesion revascularization rates at 1 year were 18.3% and 14.9%, respectively (absolute treatment difference, -3.3%; 95% CI, -13.0% to 6.4%; P=0.595). No statistically significant difference between treatment groups was observed at 12 months in the improvement by at least 1 Rutherford category of peripheral arterial disease.\n In the present study of patients with short superficial femoral artery lesions, the hypothesized absolute difference of 20% in binary restenosis at 1 year between the implantation of a single Luminexx nitinol stent and stand-alone PTA could not be demonstrated. A smaller difference requiring a larger trial might have been missed.", "Outcome with selective or systematic stenting with the Palmaz vascular stent was compared in patients with limb-threatening ischemia or persistent disabling claudication despite medical therapy, with less than 7 cm stenosis or occlusion of the superficial femoral artery.\n This was a multicenter prospective randomized trial with centralized allocation of treatment and independent review of vascular events. The primary end point was presence of more than 50% stenosis at 1-year angiographic follow-up. Secondary end points were survival; occurrence of vascular events in the treated leg; and number of failed procedures, defined as more than 50% stenosis or death at 1 year.\n Two hundred twenty-seven patients were enrolled in the study, 112 in the selective stent group, and 115 in the systematic stent group. Seventeen patients (15%) in the selective stent group received a stent after suboptimal results of percutaneous transluminal angioplasty. Angiograms for 140 patients were available at 1-year follow-up and demonstrated no statistical difference between the two groups; more than 50% stenosis of the dilated site was noted in 21 of 65 patients (32,3%) in the selective stent group and 26 of 75 patients (34.7%) in the systematic stent group (P =.85, Fisher exact test). Survival in the percutaneous transluminal angioplasty and stent groups was, respectively, 92% and 96% at 1 year, 89% and 93% at 2 years, and 82% and 80% at 4 years (P =.40, log-rank test). Survival free of new vascular events in the treated limb was 77% and 65% at 1 year, 70% and 53% at 2 years, and 57% and 44% at 4 years (P =.017, log-rank test). Number of failed procedures at 1 year was 29 of 86 (33%) and 30 of 89 (34%) (P = 0.9).\n Systematic stenting of short stenosis or occlusion of the superficial femoral artery is not justified. Palmaz vascular stent placement should be reserved for use in patients with suboptimal results of balloon angioplasty.", "A randomized pilot study was performed comparing conventional balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA] group) and rotational atherectomy (RA) with a medium size burr (50% to 70% burr/artery ratio) with systematic adjunctive balloon angioplasty (RA group) in type B2 stenosis. A total of 64 patients were included. Primary success was 93.7% in the RA group and 87.5% in the PTCA group (p = NS). Technical failure with no complication occurred once in each group. Acute complications occurred in three patients in the PTCA group and in one in the RA group. Angiographic restenosis rates were similar (RA group: 39%, PTCA group: 42%, p = NS) with a follow-up rate of 93%. In type B2 lesions, when compared with conventional angioplasty, RA with systematic balloon angioplasty does not seem to increase procedural success, and the restenosis rate remains comparable. However, these results must be confirmed in a larger series of patients." ]

[ "8671131", "1390143", "2303961", "9228227", "7546114", "16984453", "15580451", "2263919", "1793238" ]

[ "A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration.", "A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial.", "Effect of low frequency pulsing electromagnetic fields on skin ulcers of venous origin in humans: a double-blind study.", "Low-frequency ultrasound treatment of chronic venous leg ulcers in an outpatient therapy.", "The effects of non-thermal pulsed electromagnetic energy on wound healing of pressure ulcers in spinal cord-injured patients: a randomized, double-blind study.", "Low-frequency ultrasound treatment of chronic venous ulcers.", "[Venous leg ulcers: no improvement of wound healing with 685-nm low level laser therapy. Randomised, placebo-controlled, double-blind study].", "Pulsed ultrasound does not improve healing of venous ulcers.", "Low-power HeNe laser treatment of venous leg ulcers." ]

[ "The aim was to establish the potential efficacy, tolerability and side-effect profile of electromagnetic therapy as an adjunct to conventional dressings in the treatment of venous leg ulcers.\n A prospective, randomized, double blind controlled clinical trial was carried out in a dedicated leg ulcer clinic based in one urban general practice. Nineteen patients with leg ulcers of confirmed venous aetiology were assessed. The main outcome measures were rate and scale of venous leg ulcer healing, changes in patient-reported pain levels, quality of life, degree of mobility, side effect profile and acceptability to patients and staff.\n Sixty-eight per cent of patients attending this dedicated clinic achieved improvements in the size of their ulcer (4, 21%, healed fully) and in reduced pain levels (P < 0.05) during the trial, despite the chronicity of ulcer histories. Patients treated with electromagnetic therapy at 800 Hz were found at day 50 to have significantly greater healing (P < 0.05) and pain control (P < 0.05) than placebo therapy or treatment with 600 Hz. All patients reported improved mobility at the end of the study. The electromagnetic therapy was well tolerated by patients, with no differences between groups in reporting adverse events, and proved acceptable to staff.\n Despite the small numbers in this pilot study, electromagnetic therapy provided significant gains in the healing of venous leg ulcers and reduction in pain.", "A prospective, randomized, double-blind, placebo-controlled multicentre study assessed the clinical efficacy and safety of pulsed electromagnetic limb ulcer therapy (PELUT) in the healing of recalcitrant, predominantly venous leg ulcers. The portable device was used at home for 3 h daily during this 8-week clinical trial as an adjunct to a wound dressing. Wound surface area, ulcer depth and pain intensity were assessed at weeks 0, 4 and 8. At week 8 the active group had a 47.7% decrease in wound surface area vs. a 42.3% increase for placebo (P < 0.0002). Investigators' global evaluations indicated that 50% of the ulcers in the active group healed or markedly improved vs. 0% in the placebo group, and 0% of the active group worsened vs. 54% of the placebo group (P < 0.001). Significant decreases in wound depth (P < 0.04) and pain intensity (P < 0.04) favouring the active group were seen. Patients whose ulcers improved significantly after 8 weeks were permitted to continue double-blind therapy for an additional 4 weeks. Eleven active and one placebo patient continued therapy until week 12, with the active treatment group continuing to show improvement. There were no reports of adverse events attributable to this device. We conclude that the PELUT device is a safe and effective adjunct to non-surgical therapy for recalcitrant venous leg ulcers.", "The effect of an electromagnetic field on the healing of skin ulcers of venous origin in humans has been investigated in a double-blind study. Forty-four patients have been admitted to the study; one-half were exposed to active stimulators (experimental group) and the remaining to dummy stimulators (control group). The stimulation was scheduled to last a maximum of 90 days. The success rate was significantly higher in the experimental group both at day 90 (p less than 0.02) and in the follow-up period (p less than 0.005). The data suggest that the effect of the electromagnetic field lasts even when the stimulation is over. No ulcers worsened in the experimental group, while four worsened in the control group. Twenty-five percent of the patients in the experimental group and 50% in the control group experienced recurrence of the ulcer. It is concluded that stimulation with an electromagnetic field is a useful adjunctive therapy in the management of these patients.", "Low-dose ultrasound seems to be an effective method to enhance wound healing, particularly in chronic venous leg ulcers. The aim of our investigation was to examine the effect of 30 kHz low-dose ultrasound in local treatment of chronic venous leg ulcers, when added to conventional therapy of outpatients. Twenty-four patients with chronic ulcerations of the leg due to chronic venous insufficiency were randomised in placebo-controlled parallel groups in a single-blind clinical study. Patients were randomised to conventional therapy with topical application of hydrocolloid dressings and compression therapy or conventional therapy with additional ultrasound treatment for 12 weeks. The ultrasound treatment consisted of 10 min of footbathing, with application of 30 kHz continuous ultrasound 100 mW/cm2 three times a week. The ulcer area was measured by planimetry, using a millimeter grid before treatment and after 2, 4, 6, 8, 10 and 12 weeks of therapy. The ulcer radius and the daily ulcer radius reduction were calculated. Colour photographs of the ulcers were taken under standard conditions at the same time. After each treatment local findings and side effects were recorded. After 12 weeks of treatment the control group showed a mean decrease of 16.5% in the ulcerated area. In contrast the mean ulcerated area decreased by 55.4% in the ultrasound group (p<0.007). The daily ulcer reduction in the ultrasound-treated patients was 0.08 mm+/-0.04 mm and in the placebo patients 0.03 mm+/-0.03 mm. Patients recorded only minor side-effects such as a tingling feeling and occasionally pinhead-sized bleeding in the ulcer area. The application of low-frequency and low-dose ultrasound is a helpful treatment option in chronic venous leg ulcers, especially if they do not respond to conventional ulcer treatment.", "The objective of this randomized, double-blind study was to determine if non-thermal pulsed electromagnetic energy treatment significantly increases the healing rate of pressure ulcers in patients with spinal cord injuries. Subjects included volunteers admitted to a Veteran's Administration Hospital in New York over a 2 year period and consisted of 30 male spinal cord-injured patients, 20 with Stage II and 10 with Stage III pressure ulcers. Subjects were given non-thermal pulsed high-frequency electromagnetic energy treatment for 30 minutes twice daily for 12 weeks or until healed. The percentage of pressure ulcers healed was measured at one week. Of the 20 patients with Stage II pressure ulcers, the active group had a significantly increased rate of healing with a greater percentage of the ulcer healed at one week than the control group. After controlling for the baseline status of the pressure ulcer, active treatment was independently associated with a significantly shorter median time to complete healing of the ulcer. Stage III pressure ulcers healed faster in the treatment group but the sample size was limited. For spinal cord-injured men with Stage II pressure ulcers, active non-thermal pulsed electromagnetic energy treatment significantly improved healing.", "In a randomized controlled clinical trial, the properties of low-frequency ultrasound in the treatment of chronic venous ulcers were investigated. Thirty-eight patients with chronic ulcerations of the legs caused by chronic venous insufficiency were randomly assigned to receive either conventional therapy alone or conventional therapy plus additional 30 kHz ultrasound treatment. Patients with other conditions that may impair wound healing such as diabetes mellitus or arterial disease were excluded. The ultrasound treatment consisted of 10 minutes of foot bathing with application of 30 kHz ultrasound 100 mW/cm(2) three times a week. Response was evaluated with the use of planimetry of the ulcer area and compared with controls after 3 and 8 weeks. After 3 weeks of treatment (and to a greater extent after 8 weeks of treatment) the ultrasound group showed a markedly better response than the control group. Although the control group showed a mean decrease of 11% in the ulcerated area after 8 weeks, in the ultrasound group the mean ulcerated area decreased by 41% (p < 0.05). There were only mild side effects in some of the patients treated with ultrasound. In conclusion, application of low-frequency ultrasound may be a helpful treatment option in chronic venous leg ulcers.", "Venous leg ulcers (ulcera crurum venosa) are frequently seen in elderly patients. It has been suggested that low level laser irradiation has a biostimulative and wound healing effect; however, this has not yet been clinically verified by controlled studies.\n The difference in size reduction of leg ulcers with and without low level laser or placebo laser treatment was measured in 44 patients randomised into two treatment groups (685-nm low level laser and placebo laser) or a control group which served to quantify the effect of laser application. All patients received standardized wound care.\n The aim of the study was to compare the effectiveness of low level laser irradiation with that of a placebo \"light source\". The size of the ulcers was planimetrically measured at baseline (day 1), at the end of therapy (day 28) and 2 months later (day 90). The difference in wound size was evaluated.\n There were no statistically significant differences in reduction of wound size between the three groups, thus suggesting that low level laser light does not have any stimulatory effect on wound healing in ulcera crurum venosa.", "A controlled study of the effects of pulsed ultrasound was carried out in conjunction with a standard treatment for healing chronic leg ulcers on 44 patients divided randomly into two groups. All patients received standard treatment (paste impregnated bandage and a self-adhesive elastic bandage) plus placebo-ultrasound or pulsed ultrasound (1:9, 0.5 watt/cm2 at 1 MHz, for 10 min) 3 days a week for 4 weeks, thereafter twice weekly for 4 weeks and once weekly for the following 4 weeks. Percentage healed ulcer area and comparison of percentage healed ulcers were examined after 4, 8 and 12 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the pulsed ultrasound group as compared with the placebo group.", "Clinical observations have suggested that low-energy lasers, mainly helium-neon (HeNe) lasers, might stimulate wound healing. A controlled study of the effects of low-power HeNe laser was performed in conjunction with a standard treatment for healing chronic venous leg ulcers on 46 patients divided randomly into two groups. All patients received standard treatment (paste-impregnated bandage and a self-adhesive elastic bandage) plus either HeNe laser (wave-length, 632.8 nm; beam power, 6 mW; continuous emission, energy density, 4 J/cm2) or placebo HeNe laser twice weekly for 12 weeks. The areas of healing were examined and compared percentage-wise after 2, 4, 6, 8, and 12 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the HeNe group compared with the placebo group." ]

[ "20729710", "21239049", "17655918", "15389189", "16713457", "15108041", "16403097", "12437457", "14669314" ]

[ "A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod.", "Treatment of vulvar intraepithelial neoplasia with topical imiquimod: seven years median follow-up of a randomized clinical trial.", "Topical imiquimod can reverse vulvar intraepithelial neoplasia: a randomised, double-blinded study.", "Imiquimod 5% cream for the treatment of actinic keratosis: results from a phase III, randomized, double-blind, vehicle-controlled, clinical trial with histology.", "Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen's disease): a randomized, double-blind, placebo-controlled trial.", "Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur.", "Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial.", "A randomized, double-blind, vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses.", "Comparative evaluation of immune response after laparoscopical and open total mesorectal excisions with anal sphincter preservation in patients with rectal cancer." ]

[ "To determine whether imiquimod was more effective than placebo for the treatment of high-grade anal canal intraepithelial neoplasia (HG-ACIN).\n Double-blind, randomized placebo-controlled clinical trial.\n Sixty-four HIV-positive patients were randomized to self-application of imiquimod cream or matched placebo into the anal canal three times a week for 4 months. Response was assessed by cytology, high-resolution anoscopy and biopsy 2 months after therapy. All patients who failed to resolve were offered treatment with open-label imiquimod for a further 4 months.\n Fifty-three patients completed the study, of which 28 patients were on active drug and 25 patients on placebo. In the imiquimod group, four patients resolved and eight patients downgraded to low-grade squamous intraepithelial lesion (LSIL) with a median follow-up of 33 months. In the placebo group, one patient resolved. Imiquimod was significantly associated with a positive outcome (P = 0.003). Only one patient discontinued owing to side effects. Twenty-one patients entered a second open-label phase of treatment. Five of these patients cleared their anal canal intraepithelial neoplasia (ACIN) and four patients downgraded to LSIL. The overall mean duration of follow-up was 36 months. During this extended follow-up period, 61% have exhibited sustained absence of high-grade squamous intraepithelial lesion (HSIL).\n This study demonstrates the effectiveness of imiquimod for the treatment of ACIN, and the benefit of prolonged or repeated treatments. This form of therapy is likely to be especially valuable for patients with widespread multifocal ACIN who are otherwise difficult to treat, and should be considered as an adjunct to ablative therapy.", "Recently we reported on the efficacy of imiquimod for treating vulvar intraepithelial neoplasia (VIN) in a placebo-controlled, double-blinded randomized clinical trial (RCT). Four weeks after treatment, a complete response was observed in 35% of patients and a partial response in 46%. All complete responders remained disease-free at 12 months follow-up. In the current investigations, we assessed long-term follow-up at least 5 years after the initial RCT.\n Twenty-four of 26 imiquimod-treated patients who had participated in the initial RCT were seen for follow-up. Primary endpoint was durability of clinical response to imiquimod assessed by naked eye vulvar examination and histology. Long-term clinical response was correlated to lesion size before start of the initial RCT. Secondary endpoints were mental health, global quality of life, body image and sexual function in relation with long-term clinical response.\n Median follow-up period was 7.2 years (range 5.6-8.3 years). VIN recurred in one of nine complete responders. Of the initial partial responders, two became disease-free after additional imiquimod treatment. In the other partial responders, VIN recurred at least once after the initial RCT. In long-term complete responders, lesion size at study entry was smaller and these patients had a significantly better global quality of life at follow-up than patients with residual disease and/or recurrence after imiquimod treatment.\n In case of a complete response, imiquimod is effective in the long-term. Furthermore, patients with a long-term complete response had a significantly better global quality of life than patients who recurred after imiquimod treatment.\n Copyright © 2010 Elsevier Inc. All rights reserved.", "To investigate the effect of topical imiquimod in patients with vulvar intraepithelial neoplasia (VIN).\n We used a prospective, randomised, double-blinded, placebo-controlled study. Women with biopsy verified, visible VIN2 or VIN3, in a biopsy not older than 2 months were considered.\n Thirty-two patients were included, one was excluded before treatment. Twenty-one received active treatment, 10 received placebo. Seventeen (81%) in the treatment group showed complete response, two (10%) partial response and none responded in the placebo-group when evaluated by a biopsy 2 months after a treatment period of 16 weeks. Fourteen of 21 patients (67%) in the treatment group had to reduce the number of applications due to local side-effects.\n The topical treatment with imiquimod 5% was shown in this setting to be very efficient. Local side effects were a common feature, but tolerable after dose reduction. Long-term results are not known, but a planned cohort study of this population will show the rate of recurrences.", "Increasing evidence suggests imiquimod may be a safe therapeutic option for the treatment of actinic keratosis (AK). The diagnosis and assessment of most AK lesions is made clinically, without histologic confirmation.\n A phase III, randomized, double-blind, parallel group, vehicle-controlled study evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp including pretreatment and posttreatment biopsy specimens.\n A total of 286 patients at 18 centers in 6 European countries with histologically confirmed AK were randomized to either imiquimod 5% cream or vehicle cream. Study cream was applied once per day, 3 days per week, for 16 weeks. Clearance of AK lesions was clinically and histologically assessed at an 8-week posttreatment visit.\n The complete clearance rate for the imiquimod group was 57.1% versus 2.2% for the vehicle group (P <.001). The partial clearance rate (> or =75% reduction in baseline lesions) for the imiquimod group was 72.1% versus 4.3% for the vehicle group (P <.001). The most common side effects were erythema, scabbing/crusting, and erosions/ulceration. For the imiquimod group the incidence of severe erythema, scabbing/crusting, or erosions/ulceration was 30.6%, 29.9%, and 10.2%, respectively.\n Imiquimod 5% cream used 3 times per week for 16 weeks is an effective treatment for AK. Clinical clearance was established by both clinical observation and histologic analysis.", "We conducted a double-blind, placebo-controlled, randomized trial to evaluate the preliminary efficacy and safety of imiquimod 5% cream treatment for cutaneous squamous cell carcinoma (SCC) in situ.\n In all, 31 patients with biopsy-proven cutaneous SCC in situ were randomly assigned to placebo (vehicle) (n = 16) or imiquimod 5% cream (n = 15) daily for 16 weeks. Patients were assessed at week 28 for the primary end point, resolution of cutaneous SCC in situ.\n Of the 31 patients enrolled, 3 dropped out. Intention-to-treat analysis revealed 11 of the 15 patients (73%) in the imiquimod group achieved resolution of cutaneous SCC in situ, with no relapse during the 9-month follow-up period; none in the placebo group achieved resolution (P < .001). Imiquimod 5% cream was generally well tolerated and there were no serious adverse events.\n Topical imiquimod 5% cream has proven to be an effective treatment for cutaneous SCC in situ. However, studies to define the ideal dosing regimen and cost-effectiveness are required before it can be accepted as a recognized therapy.\n In this controlled trial, patients with cutaneous SCC in situ receiving topical imiquimod 5% cream as monotherapy experienced a high degree of clinical benefit compared with placebo.", "We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).\n Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2).\n A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group > chemotherapy group > control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups.\n The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).", "Imiquimod 5% cream is a topically applied immune response modifier that has been shown to give effective treatment of actinic keratosis (AK). The therapeutic effects of imiquimod are likely to involve the provocation of a cutaneous immune response against abnormal cells, an assumption based on a strong correlation between complete clearance rates and the severity of the local skin reactions (erythema, oedema, erosion/ulceration, weeping/exudation and scabbing/crusting); however, no clinical studies have conclusively proved this mechanism.\n To determine the nature of cellular infiltrates induced by the application of imiquimod to AK lesions and to study cells involved in the cutaneous immune response.\n Eighteen patients participated in this phase I, randomized, double-blind, parallel group, vehicle-controlled study. Enrolled patients were randomized in a 2 : 1 ratio to receive imiquimod cream or vehicle cream and applied study cream to five lesions on the scalp, forearm or upper trunk once daily, three days per week for up to 16 weeks. Each patient had punch biopsies of two distinct AK lesions: a lesion was biopsied before treatment to obtain baseline biomarker levels, and a different lesion was biopsied after 2 weeks of treatment. Biopsy specimens were examined using routine and immunohistochemical staining.\n The imiquimod group showed statistically significant increases from baseline to week 2 in tissue biomarker levels for CD3, CD4, CD8, CD11c, CD86/CD11c, CD68, HLA-DR and TUNEL. No significant differences were seen for the vehicle group. Complete clearance of all treated AK lesions was achieved in five of 11 (45%) imiquimod patients and in none of six vehicle patients.\n Imiquimod stimulates a cutaneous immune response characterized by increases in activated dendritic cells and CD4+ and CD8+ T cells.", "Actinic keratoses (AKs) are precancerous epidermal lesions found most frequently on areas of the skin exposed to the sun. Several case studies published recently have indicated that 5% imiquimod cream, currently licensed for the treatment of genital warts, may be an effective treatment for AK.\n To assess the efficacy and safety of imiquimod for the treatment of AK.\n Patients in this randomized, double-blind, vehicle-controlled study applied 5% imiquimod cream or vehicle to AK lesions 3 times per week for a maximum of 12 weeks or until lesions had resolved. In the event of an adverse reaction, application of imiquimod was reduced to 1 or 2 times per week. Rest periods were also allowed if necessary.\n A specialized outpatient dermatology clinic within a state-funded hospital in Germany.\n The study population was aged 45 to 85 years. Of 52 patients screened, 36 men and women with AK confirmed by histological diagnosis were enrolled. Patients were excluded from the study if they did not have a histological diagnosis for AK, if they were older than 85 years, or if they did not comply with the protocol. All patients had responded to a notice asking for volunteers.\n The number and appearance of lesions were evaluated before, during, and after treatment. All adverse effects were recorded.\n Lesions treated with 5% imiquimod cream were clinically cleared in 21 (84%) of 25 patients and partially cleared in 2 (8%). Clearance was histologically confirmed 2 weeks after the last application of imiquimod in all patients clinically diagnosed as lesion free. Only 10% of patients treated with imiquimod were clinically diagnosed with recurrence 1 year after treatment. No reduction in the size or number of AK lesions was observed in vehicle-treated patients. Adverse effects reported by patients treated with imiquimod included erythema, edema, induration, vesicles, erosion, ulceration, excoriation, and scabbing. However, imiquimod was well tolerated since all patients completed the 12-week treatment. Only a few, mild adverse reactions to the vehicle cream were reported.\n Application of 5% imiquimod cream for 12 weeks is an effective and well-tolerated treatment for AK.", "The study of immune response of open versus laparoscopical total mesorectal excision with anal sphincter preservation in patients with rectal cancer has not been reported yet. The dissected retroperitoneal area that contacts directly with carbon dioxide is extensive in laparoscopic total mesorectal excision with anal sphincter preservation surgery. It is important to clarify whether the immune response of laparoscopic total mesorectal excision with anal sphincter preservation (LTME with ASP) in patients with rectal cancer is suppressed more severely than that of open surgery (OTME with ASP). This study was designed to compare the immune functions after laparoscopic and open total mesorectal excision with anal sphincter preservation for rectal cancer.\n This study involved 45 patients undergoing laparoscopic (n=20) and open (n=25) total mesorectal excisions with anal sphincter preservation for rectal cancer. Serum interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha) were assayed preoperatively and on days 1 and 5 postoperatively. CD3+ and CD56+ T lymphocyte count, CD3- and CD56+ natural killer cell (NK) count and immunoglobulin (IgG/IgM/IgA) were assayed preoperatively and on day 5 postoperatively. The numbers of CD3+ and CD56+ T lymphocytes and CD3- and CD56+ NK cells were counted using flow cytometry. An enzyme-linked immunosorbent assay (ELISA) was used for IL-2, IL-6 and TNFalpha determination. And IgG, IgM, and IgA were assayed using immunonephelometry.\n The demographic data of the two groups had no difference. The preoperative levels of CD3+ and CD56+ T lymphocyte count, CD3- and CD56+ NK count, serum IgG, IgM, IgA, IL-2, IL-6 and TNFalpha also had no significant difference in the two groups (P>0.05). The CD3+ and CD56+ T lymphocyte counts had no obvious changes after surgery in laparoscopic (d=-0.79 +/- 3.83%) and open (d=0.42 +/- 2.09%) groups. The CD3- and CD56+ NK counts were decreased postoperatively in both laparoscopic (d=-7.23 +/- 11.33%) and open (d=-9.21 +/- 13.93%) groups. The differences of the determined values of serum IgG, IgM and IgA on the fifth day after operation subtracted those before operation were -2.56 +/- 2.14 g/L, -252.35 +/- 392.94 mg/L, -506.15 +/- 912.24 mg/L in laparoscopic group, and -1.81 +/- 2.10 g/L, -282.72 +/- 356.75 mg/L, -252.20 +/- 396.28 mg/L in open group, respectively. The levels of IL-2 were decreased after operation in both groups. However, the levels of IL-6 were decreased after laparoscopic surgery (d1=-23.14 +/- 263.97 ng/L and d5=-40.08 +/- 272.03 ng/L), and increased after open surgery (d1=27.38 +/- 129.14 ng/L and d5=21.67 +/- 234.31 ng/L). The TNFalpha levels were not elevated after surgery in both groups. There were no significant differences in the numbers of CD3+ and CD56+ T lymphocytes and CD3- and CD56+ NK cells, the levels of IgG, IgM, IgA, IL-2, IL-6 and TNFalpha between the two groups (P>0.05).\n There are no differences in immune responses between the patients having laparoscopic total mesorectal excision with anal sphincter preservation and those undergone open surgery for rectal cancer." ]

[ "1892197", "2659132", "16765169", "3382883", "11023726", "7806870", "12174159", "6244414", "2487304" ]

[ "Effectiveness of antibiotic prophylaxis in preventing bacteriuria after multichannel urodynamic investigations: a blind, randomized study in 124 female patients.", "Are prophylactic antibiotics necessary during extracorporeal shockwave lithotripsy?", "Effectiveness of ciprofloxacin prophylaxis in preventing bacteriuria caused by urodynamic study: a blind, randomized study of 192 patients.", "Is antibiotic prophylaxis necessary for routine urodynamic investigations? A controlled study in 100 patients.", "Could the incidence of postoperative urinary tract infection be reduced by reversing the sequence of vaginal cleansing and urethral catheterization?", "Antibiotic prophylaxis for urodynamic testing in patients with spinal cord injury: a preliminary study.", "Value of urinary prophylaxis with methenamine in gynecologic surgery.", "Prophylaxis of bacteriuria during intermittent catheterization of the acute neurogenic bladder.", "[Acute cystourethritis during pregnancy]." ]

[ "One hundred twenty-four women with chronic, persistent lower urinary tract symptoms who had been scheduled for elective urodynamic investigations at Mount Sinai's Urodynamic Investigative Unit were divided into two blind, randomized groups, receiving either a placebo or prophylactic antibiotic. At the time of urodynamic testing, the rate of unsuspected urinary tract infection was 8.1%. There was no statistically significant decrease in postinstrumentation infection rate in the group who received prophylactic antibiotics. We conclude that, given in the fashion described in the study, prophylactic antibiotics are not effective in preventing urinary tract infections caused by urodynamic testing.", "A randomised clinical study was carried out on patients admitted for ESWL treatment in order to establish the requirement for prophylactic treatment with antibiotics during this procedure. Patients with clinical signs of urinary tract infection, evidence of infectious stones or a positive urine culture were excluded. All other patients were consecutively randomised into 3 groups which were given either trimethoprim + sulphamethoxazole or mecillinam (Group A), methenamine hippurate (Group B), or no treatment at all (Group C). Evaluation with respect to clinical signs of infection was done immediately after the treatment and 4 weeks later. In addition, a urine culture was performed 2 weeks after ESWL, i.e. 1 week after completing treatment with antibiotics and methenamine hippurate. With respect to infectious complications there were no differences between Groups A and C, between Groups B and C or between Group A and B+C, whereas an unexplained slightly higher infectious rate was recorded for Group B compared with Group A. In all patients the occurrence of bacteriuria was low (6.7%) despite the fact that almost 30% of patients had a ureteric catheter during the ESWL procedure. Patients with ureteric catheters did not present with more infectious complications than those without. All patients had a bladder catheter during ESWL. It was concluded that prophylactic treatment with antibiotics during ESWL treatment is unnecessary in all situations where an infectious aetiology is unlikely.", "To determine the efficacy of prophylactic ciprofloxacin in preventing urinary tract infections caused by urodynamic study (UDS).\n A total of 210 patients presenting for UDS during a 16-month period were offered enrollment in the study. A clean-catch midstream urine sample was taken 24 hours before and 48 to 72 hours after the procedure and after microscopic examination and culture were done. All patients underwent a standard UDS. The 192 patients who had sterile urine before intervention were included in the study. Randomly, 98 of the 192 patients were orally given 500 mg of ciprofloxacin 1 hour before the urodynamic intervention and 94 were not given anything. The patients who were found to have significant bacteriuria after UDS were followed up and treated properly.\n Eighteen patients (8.6%) who had significant bacteriuria in the urine culture before UDS were excluded from the study. The rate of significant bacteriuria in the urine culture after UDS was 7.3% overall, 1% in the prophylaxis group, and 14% in the controls, a significant difference (P = 0.002). The most common uropathogen was Escherichia coli (57%). Three independent risk factors were identified: not giving antibiotic prophylaxis before UDS; antibiotic use in the preceding month; and the presence of pyuria before UDS.\n Urinary tract infections after UDS decreased from 14% to 1% with a single dose of ciprofloxacin 500 mg orally before UDS. We recommend antibiotic prophylaxis for patients undergoing a UDS.", "The value of a prophylactic antibiotic before a routine cystometrogram has been assessed in a controlled trial of 100 patients. The infection rate was low and not statistically different in both groups. Subsequent symptoms of dysuria and haematuria had a mechanical aetiology.", "Postoperative urinary tract infection (UTI) is a common hospital infection after gynaecological operations. A prospective randomized study was performed to examine whether the incidence of UTI could be reduced by reversing the sequence of vaginal cleansing and urethral catheterization. Subjects were randomly allocated to: (1) urethral catheterization before vaginal cleansing; and (2) urethral catheterization after vaginal cleansing. Urine cultures were performed immediately after the procedures as the baseline, on the day of catheter removal, and two days after catheter removal. Patients were examined daily after the operation for any urinary symptoms and fever. The incidences of preoperative asymptomatic bacteriuria were similar in both groups, seven of 84 in group 1 vs. eight of 83 in group 2. Among those with negative urine culture before the operation, 77 in group 1 and 75 in group 2, there was no significant difference in postoperative bacteriuria at catheter removal (23 vs. 22) and two days later (35 vs. 42). No significant difference was noted in the incidence of UTI (5 vs. 10, P = 0.25), with a trend towards less UTI in group 1. Voiding discomfort was more common, and fever less common in group 1. There were significant associations between urine culture results at three different occasions. Bacteriuria at catheter removal is associated with a 7.2 times risk of bacteriuria two days later, 2.4 times risk of urinary symptoms and 3.2 times risk of UTI. Routine surveillance at catheter removal is not cost-effective. We conclude that postoperative bacteriuria and UTI are common. Reversing the sequence of the procedures cannot reduce the incidence. There is no evidence to change the status quo.", "This study was performed in order to: (i) determine the incidence of symptomatic urinary tract infection (UTI) in patients with spinal cord injury after urodynamic testing; (ii) evaluate the role of antibiotic prophylaxis for such a procedure; and (iii) investigate whether pre-existing bacteriuria predisposes to the development of symptomatic UTI after urodynamic testing. Forty patients were prospectively randomized in a double-blind fashion to receive a 3-day oral course of either ciprofloxacin (18 patients) or placebo (22 patients), beginning 2 days prior to the urodynamic procedure. None of 18 (0%) patients who received ciprofloxacin developed symptomatic UTI within 5 days after the procedure compared with three of 22 (14%) subjects randomized to the placebo group; the protective efficacy of antibiotic prophylaxis, however, did not attain statistical significance (P = 0.24). None of the three bacterial isolates that were responsible for symptomatic infection were grown in corresponding urine cultures prior to the procedure. These findings may serve as a pilot for a larger study.", "There is a high risk of postoperative bacteriuria and urinary tract infection after gynecologic surgery. Postoperative asymptomatic bacteriuria often disappears without treatment, but 15-20% of patients still require treatment for postoperative urinary tract infection. This study was carried out to assess the value of prophylactic treatment with methenamine hippurate after routine gynecologic surgery.\n This was a prospective, randomized, double-blind, placebo-controlled clinical trial comprising 145 patients undergoing routine gynecologic laparotomy or vaginal plastic surgery using a Foley catheter for 24 h. Antibiotics were not used. Subjects received 1 g Hiprex or placebo twice daily for 5 days. Urine was cultured preoperatively, at catheter removal, and 2 days later. Patients with positive cultures were not given antibiotics unless they were symptomatic. The follow-up period was 1 month.\n The chi-square test, Fisher exact test, and t-test were used with level of significance at 0.05, and odds ratios with 95% confidence intervals were calculated.\n Asymptomatic bacteriuria was diagnosed in 36 cases (50.0%) in the placebo group and 22 cases (30.1%) in the methenamine group (p = 0.02). Urinary tract infection was diagnosed in 10 cases (13.9%) in the placebo group and two cases (2.7%) in the methenamine group (p = 0.03). There were few adverse events.\n Prophylactic treatment with methenamine hippurate significantly reduces the incidence of postoperative bacteriuria and urinary tract infection.", "A randomized prospective study of bacteriuria control during early intermittent bladder catheterization was performed on a spinal cord injury service. The 64 male subjects underwent 16,620 catheterizations and had 83 significant episodes of infection. The infection rates among various groups were compared: 1) control patients, 2) patients treated with intravesical neomycin/polymyxin-B, 3) patients given low dose daily macrocrystals of nitrofurantoin and 4) patients given intravesical treatment and oral nitrofurantoin. There was significant reduction in infection rates when oral and intravesical antibiotics were used.", "A prospective study was carried out in 103/863 obstetric patients with cystitis characterized by urinary urgency and frequency, dysuria, pyuria and suprapubic discomfort in the absence of systemic symptoms such as fever and costovertebral angle tenderness. The association of symptomatic lower urinary tract infection with low-count bacteriuria (10(2)-10(5) UFC/mL of urine) was present in all the patients. The incidence of cystourethritis was about 12%, most of the infections occurred at the first trimester. To learn whether a multiple-dose of nitrofurantoin or ampicillin is safe and effective therapy for acute uncomplicated urinary tract infections, 103 symptomatic pregnant women were randomly grouped to receive oral nitrofurantoin (100 mg t.i.d.) or ampicillin (500 mg t.i.d.) for five days. Seventeen patient were excluded since they did not return for follow-up. Escherichia coli was isolated in 67% of infections. Overall cure varied from 87% to 89%, without any great differences between the regimens. Nine patients had asymptomatic bacteriuria in the course of pregnancy, four developed acute pyelonephritis and one of them had abnormal intravenous pyelogram." ]

[ "3788652", "1681680", "3322467", "1684310", "4011672", "7870975", "6371871", "11442893", "11738537" ]

[ "Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison.", "Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study.", "Haloperidol decanoate v. fluphenazine decanoate as maintenance therapy in chronic schizophrenic in-patients.", "Minimal effective dose and relapse--double-blind trial: haloperidol decanoate vs. placebo.", "Double-blind comparison of haloperidol decanoate and fluphenazine decanoate effectiveness, side-effects, dosage and serum levels during a six months' treatment for relapse prevention.", "Addition of lithium to haloperidol in non-affective, antipsychotic non-responsive schizophrenia: a double blind, placebo controlled, parallel design clinical trial.", "A double-blind, controlled clinical trial of haloperidol decanoate and fluphenazine decanoate in the maintenance treatment of schizophrenia.", "Olanzapine versus haloperidol in the treatment of patients with chronic schizophrenia: results of the Japan multicenter, double-blind olanzapine trial.", "Does cognitive function improve with quetiapine in comparison to haloperidol?" ]

[ "Thirty-two schizophrenic patients, previously treated with antipsychotics, were treated with haloperidol decanoate and flupenthixol decanoate in a double-blind cross-over study. The drugs were given for 24 weeks each at an individually adapted dose. The last three injections of either drug were given at fixed 4-week intervals. The mean dose over the two treatment periods changed from 131 mg (start) to 151 mg (week 24) in the haloperidol decanoate group and from 56 mg to 66 mg in the flupenthixol decanoate group, the inter-drug ratio being 2.3:1. During the first study period, the patients' condition remained rather stable with both drugs. After crossing-over, the symptoms were further reduced with haloperidol decanoate but increased with flupenthixol decanoate. Side effects of the two drugs were comparable and were generally few and mild. It was concluded that 4-week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals.", "Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.", "In a double-blind study of 38 chronic schizophrenic in-patients, haloperidol decanoate was compared with fluphenazine decanoate as maintenance therapy over 60 weeks. Both drugs were given by injection at 4-week intervals. Haloperidol and fluphenazine were assumed to be equipotent; the mean starting dose of the former was 127 mg and of the latter 106 mg. The number of withdrawals over 60 weeks was similar in both groups but relapses, strictly defined, were significantly more frequent in the haloperidol group. When patients were switched to haloperidol, Parkinsonism diminished more quickly than in the fluphenazine group, but after 60 weeks there was no difference in severity in the two drug groups. The higher relapse rate and the quicker reduction in Parkinsonism in the haloperidol group might be due to a misjudgement in equivalent doses of the two drugs. Plasma haloperidol steady state levels were reached in most patients by 8-12 weeks. Plasma neuroleptic and prolactin levels, week-by-week systemic drug availability and Parkinsonism showed less variation between injections with haloperidol than with fluphenazine.", "Fifty-six chronic schizophrenic patients were randomized into haloperidol decanoate (HD) or placebo groups for 48 weeks of double-blind treatment. The double-blind trial was preceded by a 15-week single-blind run-in period, during which all patients were treated with 60 mg of HD (approximately corresponding to 3.6 mg orally/day) every fourth week (except for the second injection, which was given after 3 weeks). Eight relapses occurred during the run-in period, and seven other patients refused further participation. The remaining 41 patients were then treated double blind, either with HD, 60 mg/4 weeks (18 patients), or with placebo (23 patients). Two patients (11%) in the HD group and 16 (69%) in the placebo group relapsed during the 48-week double-blind period. The plasma concentrations of haloperidol were measured every fourth week in both groups. Steady state was reached after 11 weeks. The mean steady-state level was 6.3 nmol/L. In the placebo group, a 50% decrease in the mean haloperidol plasma concentration was seen 8 weeks after withdrawal of haloperidol. The haloperidol plasma concentration was a predictor of relapse. There was no statistical difference between the treatment groups regarding extrapyramidal symptoms. More biperiden, however, was used in the HD group, while the placebo patients took more sedatives. The results of this study show that the relatively low and fixed dose of 60 mg of HD every fourth week was superior to placebo in preventing relapse in schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)", "In this present study 31 schizophrenic patients were treated for six months for relapse prevention under double-blind conditions with either haloperidol decanoate (22) or fluphenazine decanoate (9). In respect of the prophylactic action, both depot neuroleptics proved to be equal during the comparatively short period of observation. In both groups a psychotic relapse occurred that could not be managed by increasing the depot dosage. No side-effects worth mentioning appeared in either group of patients; patients under haloperidol decanoate, however, only required half the quantity of anti-parkinson medication as compared with patients treated with fluphenazine decanoate, and also displayed extrapyramidal motor symptoms (EPMS) to a lesser degree. Patients received a mean monthly injection of 80 mg of Haloperidol, reaching steady-state serum levels of about 3 ng/ml in the third injection interval. Fluphenazine serum levels known so far for seven patients amount to 0.8 ng/ml after fluphenazine injections of 21 mg every 14 days.", "This double-blind placebo controlled, parallel design clinical trial compared the therapeutic effects of the addition of lithium or placebo to haloperidol in 21 seriously ill state hospital patients with DSM-III-R schizophrenia, who did not have concurrent affective disorders and who had not responded to previous trials of conventional antipsychotic medication. During a baseline period of 6 weeks, patients were switched to a stable dose of haloperidol (mean +/- SD dose = 13.6 +/- 8.1 mg/day). Patients were then randomized to receive either lithium or placebo in addition to haloperidol for 8 weeks (mean +/- SD lithium level = 0.98 +/- 0.13 mEq/l). Symptoms and side effects were assessed weekly. Improvement in symptoms correlated with the non-blind adjustment of antipsychotic dose, but not with lithium or placebo treatment. Side effects ratings did not differ between the two groups, but one patient developed a reversible delirium associated with combined lithium/haloperidol treatment. For these long-term, severely ill patients, combined treatment afforded no advantage over treatment with haloperidol alone.", "nan", "This randomized double-blind trial was conducted to test the efficacy and safety of olanzapine in Japanese patients with schizophrenia. Importantly, this study also represents the first large clinical trial of olanzapine conducted in an Asian population. Patients (n = 182) were randomly assigned to treatment with olanzapine or haloperidol over a period of 8 weeks. The primary analyses included: (i) a test of non-inferiority of olanzapine compared with haloperidol in efficacy using the Final Global Improvement Rating (FGIR); and (ii) comparison between the treatment groups in extrapyramidal symptom severity using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Olanzapine was comparable to haloperidol in efficacy in treating positive symptoms and significantly superior in treating negative symptoms. Extrapyramidal symptom severity was significantly improved for olanzapine-treated patients versus haloperidol-treated patients. Olanzapine was shown to be more effective and better tolerated than haloperidol in the treatment of Japanese patients suffering from chronic schizophrenia.", "Recent evidence suggests that schizophrenia patients taking atypical antipsychotic medications may perform better on some tests of cognitive function than those treated with older antipsychotics. The current study compared the effects of quetiapine and haloperidol on measures of executive function, memory and attention. Subjects were 58 stable outpatients with schizophrenia (DSM III-R) who received a battery of cognitive tests as part of a randomized, double-blind, multi-site clinical efficacy study conducted by AstraZeneca Pharmaceuticals. Cognitive assessments were conducted prior to randomization when patients were receiving < or =30 mg haloperidol or equivalent (mean: 9.2mg/day haloperidol equivalents), and again after 24 weeks of fixed-dose treatment with either quetiapine 600 or 300 mg/day or haloperidol 12 mg/day. Analyses of covariance with planned comparisons were used to compare scores on cognitive measures at the end of 24 weeks by treatment group with baseline cognitive function scores used as covariates. Patients receiving quetiapine 600 mg/day improved to a greater extent than patients receiving haloperidol on overall cognitive function (p<0.02). Specific differences were found for executive function (Verbal Fluency Test, p<0.04), attention (Stroop Color Word Test, p<.03) and verbal memory (Paragraph Recall Test, p<0.02). Treatment group differences were not solely due to benztropine use, medication side effects, or changes in symptomatology. Treatment with quetiapine at higher doses (600 mg/day) relative to haloperidol appears to have a positive impact on important domains of cognitive performance that have been found to predict role function and community outcomes in patients with schizophrenia." ]

[ "9580172", "2206065", "8238130", "9642605", "18472878", "9307346", "8238160", "1407911", "18476153" ]

[ "Administration of antibiotics to patients with rupture of membranes at term: a prospective, randomized, multicentric study. Collaborative Group on PROM.", "Antibiotic therapy in preterm premature rupture of membranes: a randomized, prospective, double-blind trial.", "Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.", "Antibiotic treatment in preterm labor and intact membranes: a randomized, double-blinded, placebo-controlled trial.", "Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor.", "Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.", "Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture.", "Expectant management of preterm ruptured membranes: effects of antimicrobial therapy.", "Chlorhexidine vs. Sterile vaginal wash during labor to prevent neonatal infection." ]

[ "To assess whether antibiotic administration changes the rate of materno-fetal infectious morbidity in premature rupture of membranes occurring later than 35 weeks of gestation.\n A prospective, randomized and multicentric study in the Perinatology Units of eleven hospitals in Spain. Women were randomized to either antibiotic administration or control group. All were induced, if labor had not started spontaneously after 12 hours of ruptured membranes. Main outcome measures were maternal infection (chorioamnionitis and endometritis) and neonatal infectious morbidity (neonatal sepsis, meningitis and bronchopneumonia).\n Seven hundred and thirty-three patients were enrolled in the study, 371 in the antibiotics group and 362 in the control group. The incidence of chorioamnionitis and puerperal endometritis were reduced but the differences are statistically nonsignificant. However, the incidence of neonatal sepsis was significantly lower in newborns to mothers who had received antibiotics, 1 vs. 7 cases (Fisher's exact test, p<0.007).\n The study strongly suggests that prophylactic use of antibiotics in premature rupture of membranes occurring at 36 or more weeks of gestation reduces the risk of neonatal sepsis and probably maternal endometritis.", "The use of antibiotics in the management of preterm, premature rupture of membranes remains controversial. By use of a prospective randomized double-blind design we investigated the maternal-fetal benefits associated with antibiotic therapy in 85 women with premature rupture of membranes at 34 weeks' estimated gestational age. In the treatment group 40 patients received intravenous mezlocillin for 48 hours followed by oral ampicillin until delivery. In the control group 45 patients received intravenous and oral placebo. Patients who received antibiotics had chorioamnionitis and endometritis less frequently than the control group (p less than 0.01 and p less than 0.05). Pathologic examination of the placentas showed a lower incidence of chorioamnionitis in the treatment group (p less than 0.05). The period from premature rupture of membranes to delivery (latency) was prolonged with antibiotics (p less than 0.05) and resulted in significant weight gain in the infants in the antibiotic group (p less than 0.0001). These infants also had higher 1- and 5-minute Apgar scores. Clinically suspected sepsis, respiratory distress syndrome, intraventricular hemorrhage, perinatal death rate, and prolonged hospitalization (greater than 30 days) were also increased in the control group.", "Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes.\n A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos.\n Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization.\n The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.", "Although an association between microbial invasion of amniotic cavity and preterm birth has been extensively demonstrated, there is conflicting evidence regarding the benefits of antibiotic therapy in patients with preterm labor and intact membranes. We attempted to assess the efficacy of amoxicillin and erythromycin on pregnancy outcome in those patients. A randomized, double-blinded, placebo-controlled trial was designed and implemented. A total of 196 patients with singleton pregnancies and preterm labor with intact membranes (22-36 weeks) were randomly allocated to receive either antibiotics or placebo, plus adjunctive parenteral tocolysis, and 173 patients (antibiotics group n = 83 vs. placebo group n = 90) completed the treatment. The overall prevalence of microbial invasion of the amniotic cavity was 5.2% (9/173). No significant difference between both groups was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery, and frequency of clinical chorioamnionitis and endometritis. Rate of cesarean section was significantly higher in the placebo group (28% vs. 12%). Regarding neonatal outcome, no significant difference was detected between both groups in neonatal death, respiratory distress syndrome, proven sepsis, and birthweight. Suspected sepsis was significantly more frequent in the placebo group (6/90 vs. 0/78). The results of this trial indicate that amoxicillin and erythromycin do not prolong pregnancy in patients with preterm labor and intact membranes. A significant reduction in the rate of cesarean section was observed in patients receiving antibiotics. A significant reduction in the rate of neonatal suspected sepsis was also demonstrated.", "The objective of this study was to assess whether antibiotic therapy plus tocolysis given to women in preterm labor would prolong pregnancy compared with tocolysis alone.\n A randomized, double-blind trial of intravenous mezlocillin and oral erythromycin therapy vs. placebo was used in addition to tocolysis among women in preterm labor < or =34 weeks gestation with intact membranes. Amniocentesis was performed, and chorioamnionic membranes were examined histologically and cultured for microorganisms after delivery.\n Clinical characteristics including gestational age at enrollment, frequency of contractions, cervical Bishop's score, and white blood cell count on admission were similar in the 2 groups. Antibiotic therapy was well tolerated. No significant differences in the interval to delivery, birth weight, and neonatal outcomes were observed between the 2 groups. Women in the antibiotic group had a significantly lower incidence of postpartum infections compared with women in the placebo group. Patients with evidence of upper genital tract infection in either group had a significantly shorter interval to delivery, lower gestational age at delivery, lower mean birth weight, and increased neonatal hospitalization time.\n Lack of an antibiotic effect on the gestational age at delivery may be due to the low prevalence of upper genital tract infection among unselected women in preterm labor, to advanced preterm labor unresponsive to antibiotic therapy, or to an inability of antibiotics given alone to inhibit the cytokine response. Further work is needed to identify markers of upper genital tract infection among women in preterm labor and to evaluate other potential therapeutic interventions.", "Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent.\n To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity.\n Randomized, double-blind, placebo-controlled trial.\n University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.\n A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization.\n Intravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization.\n The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed.\n In the total study population, the primary outcome (44.1 % vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001).\n We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.", "Our purpose was to determine whether maternal administration of prophylactic ampicillin or erythromycin after preterm amnion rupture is associated with maternal or neonatal benefits.\n Women with singleton pregnancies between 24 and 33 weeks 6 days of gestation were eligible if they had no immediate indication for delivery. After giving informed consent, patients were randomized either to receive ampicillin (erythromycin if penicillin allergic) until delivery or to enter a control group. Women whose cervical cultures were positive for either group B streptococci or Neisseria gonorrhoeae received treatment. Tocolytics and corticosteroids were not used.\n From January 1990 to February 1992 117 patients (antibiotics 59, control 58) were recruited and analyzed. Prophylactic antibiotics were associated with a longer latent phase (mean 12 vs 7.0 days, p = 0.004) and fewer maternal infectious complications (29% vs 60%, p = 0.001). A higher incidence of neonatal necrotizing enterocolitis was observed in the treatment group (14% vs 3.5%, p = 0.05). Other neonatal complications, including death, were lower in the treatment group, but none attained statistical significance (p = 0.09 to 0.33).\n The use of prophylactic antibiotics in selected patients after preterm amnion rupture appears to have a demonstrable maternal benefit. Large, multicenter trials may demonstrate a significant neonatal benefit or confirm any adverse outcomes.", "To determine whether the addition of broad-spectrum antimicrobial therapy to traditional expectant management improves pregnancy outcome in patients with premature rupture of membranes (PROM) remote from term.\n Patients with preterm PROM before 34 weeks' gestation who were not in labor and had no signs of infection or fetal distress were randomized to one of two study groups: 1) expectant management alone and 2) expectant management plus antimicrobial therapy. Women in the latter group received intravenous ampicillin, gentamicin, and clindamycin for 24 hours, followed by amoxicillin plus clavulanic acid orally for 7 days. Other than antibiotic use, management of the two groups was identical.\n Significantly more women (P < .01) treated with antibiotics (20 of 48, 42%) remained undelivered 7 days after admission compared with those managed expectantly without antibiotics (seven of 46, 15%). In addition, more neonates in the group managed with antibiotics were admitted to the routine nursery (nine of 48 versus two of 45; P = .03). However, there was no difference between the groups in the frequency of serious maternal or neonatal morbidity.\n The addition of broad-spectrum antimicrobial therapy to traditional expectant management of pregnancy complicated by preterm PROM may increase the number of gestations undelivered 7 days after admission. It may also decrease the proportion of infants admitted to special care nurseries. Whether these effects result in significant short- or long-term maternal or neonatal benefit remains to be determined.", "Objective: The purpose of this study was to determine if a dilute solution of chlorhexidine used as a one-time vaginal wash intrapartum can reduce the use of postnatal antibiotics and neonatal infection.Methods: Term pregnant women in labor were prospectively randomized to receive either 20 cc of 0.4% chlorhexidine (n = 481) or 20 cc of sterile water (n = 466) placebo. Exclusion criteria included fetal distress, clinical infection, cervical dilatation >6 cm, and known allergy to chlorhexidine. Outcome variables included the incidence of neonatal pneumonia, culture proven neonatal sepsis, and use of the antibiotics in the neonate. Continuous variables were compared using the Mann-Whitney U-test and discrete variables were compared with the chi-square test.Results: The length of ruptured membranes (mean +/- S.D.) between the chlorhexidine group (408 +/- 589 min) and control group (352 +/- 318 min) was not significantly different (P = 0.85, 95% confidence interval 354-462). Fifteen neonates (3.2%) in the chlorhexidine group and 9 (1.9%) in the control group received antibiotics in the postnatal period (P = 0.32, 95% confidence interval 0.72-3.72). There was one case of pneumonia in the control group and no cases of sepsis in either group.Conclusions: A one-time chlorhexidine vaginal wash does not decrease the use of antibiotics or incidence of neonatal infection in our population." ]

[ "16754835", "11982448", "12900300", "9169300", "15119922", "17728106", "16449469", "14971863", "11530275" ]

[ "Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.", "A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia.", "Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol.", "Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial.", "Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial.", "Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine.", "Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.", "Adverse effects and laboratory parameters of high-dose olanzapine vs. clozapine in treatment-resistant schizophrenia.", "Double-blind olanzapine vs. haloperidol D2 dopamine receptor blockade in schizophrenic patients: a baseline-endpoint." ]

[ "Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.\n To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.\n Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).\n Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).\n Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.\n Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.", "An intramuscular (IM) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia.\n Recently hospitalized acutely agitated patients with schizophrenia (N = 270) were randomized to receive 1 to 3 IM injections of olanzapine (2.5, 5.0, 7.5, or 10.0 mg), haloperidol (7.5 mg), or placebo within 24 hours. A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores 2 hours after the first injection. Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection.\n Olanzapine exhibited a dose-response relationship for reduction in agitation (F(1,179)= 14.4; P<.001). Mean PANSS-EC reductions 2 hours after the first injection of olanzapine (2.5 mg = -5.5; 5.0 mg = -8.1; 7.5 mg = -8.7; 10.0 mg = -9.4) were superior to those with placebo (-2.9; P =.01 vs olanzapine at 2.5 mg; P<.001 for each other olanzapine dose) but not with haloperidol (-7.5). A dose of 5.0, 7.5, or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection. There were no differences between treatment groups for hypotension, the most frequently reported adverse event, or for clinically relevant changes in the QTc interval. There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol (16.7%) than with 2.5 (P =.03), 5.0 (P =.03), or 7.5 mg (P =.01) of IM olanzapine (0%) or with placebo (0%) (P =.01).\n Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile.", "Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial.\n Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase.\n Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%).\n As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.", "A 6-week acute phase of an international 1-year double-blind study was conducted comparing three dose ranges of olanzapine (5 +/- 2.5 mg/day, 10 +/- 2.5 mg/day, and 15 +/- 2.5 mg/day) with a fixed dose of olanzapine (1.0 mg/day) and with a dose range of haloperidol (15 +/- 5 mg/day) in the treatment of 431 patients with schizophrenia. The purpose was to determine whether olanzapine demonstrated a dose-related ability to decrease overall psychopathology with minimal associated extrapyramidal symptoms in patients with schizophrenia. The high-dose olanzapine group showed statistically significantly greater improvement in overall psychopathology based on mean change in the CGI Severity score and statistically significantly greater improvement in positive psychotic symptoms based on mean change in both the BPRS positive score and the PANSS positive score compared with the 1.0-mg/day olanzapine group. Analyses indicated that an increasing dose-response curve was observed across the range of all olanzapine dose groups. Acute extrapyramidal syndromes were reported less frequently among all olanzapine groups compared with the haloperidol group. Endpoint mean change on both the Simpson-Angus Scale and the Barnes Akathisia Scale reflected improvement for all olanzapine treatment groups compared with worsening for the haloperidol group. Olanzapine was associated with weight gain but did not appear to have any clinically meaningful effect on vital signs. Although olanzapine was associated with some increase in prolactin concentrations, increases were transient, occurred less often, and were of lesser magnitude than those observed with haloperidol.", "The purpose of this study was to explore the efficacy of adding an atypical antipsychotic, olanzapine, to a serotonin reuptake inhibitor (SRI) in treatment-refractory obsessive-compulsive disorder (OCD).\n Twenty-six patients aged between 18 and 65 (mean = 41.2, SD = 11.9) years meeting DSM-IV criteria for OCD, who had not responded to SRIs, were treated for 6 weeks in a double-blind, placebo-controlled augmentation study with either olanzapine (up to 20 mg/day) or placebo. Severity of illness was assessed biweekly by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Analysis of covariance with baseline Y-BOCS score included as a covariate was used to compare improvement in Y-BOCS scores in the 2 groups. Response was defined as a 25% or greater improvement in Y-BOCS score. Data were collected between April 2001 and May 2003.\n Outcome was assessed for all patients using the last observation carried forward. Subjects in the olanzapine group had a mean decrease of 4.2 (SD = 7.9) in Y-BOCS score compared with a mean increase in score of 0.54 (SD = 1.31) for subjects in the placebo group (F = 4.85, df = 2,23; p =.04). Six (46%) of 13 subjects in the olanzapine group showed a 25% or greater improvement in Y-BOCS score compared with none in the placebo group. The final mean dose of olanzapine was 11.2 (SD = 6.5) mg/day. Medication was well tolerated. Only 2 (15%) of 13 subjects who received olanzapine discontinued because of side effects: sedation (N = 1) or weight gain (N = 1).\n These results provide preliminary evidence that adding olanzapine to SRIs is potentially efficacious and well tolerated in the short-term treatment of patients with refractory OCD. Controlled studies with larger sample sizes are necessary to more definitively address this treatment strategy.", "Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure.\n The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia.\n In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI).\n Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life.\n Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities.", "In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.\n The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.\n Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.\n Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.", "Patients with treatment-resistant schizophrenia pose a major challenge to caregivers since only clozapine is documented as having superior efficacy in this population. Although olanzapine is similar to clozapine in structure and receptor profile, it has not been proven to have superior efficacy for this patient group. Nonetheless, olanzapine is being increasingly used in higher doses as clinicians attempt to find a more effective and tolerable therapy for refractory patients. Furthermore, there are little data comparing olanzapine and clozapine in this population. Thirteen patients participated in a randomized double-blind 16-week crossover study of clozapine therapy (450 mg/day) compared to high doses of olanzapine (50 mg/day). No patients on olanzapine responded while 20% responded to clozapine treatment. Olanzapine patients tended to experience higher rates of anticholinergic effects such as dry mouth (80 vs. 20%) and blurry vision (40 vs. 0%). Clozapine-treated patients had higher rates of sialorrhea (80 vs. 10%), sweating (50 vs. 10%), dyspepsia (70 vs. 30%), and lethargy (90 vs. 60%). Neither treatment was associated with significant akathisia. Liver enzyme elevation and lipids were higher with clozapine treatment. Mean weight gain in the initial 8 weeks was 3.4 kg for olanzapine and 1.2 kg for clozapine. High doses of olanzapine during 8 weeks of treatment did not increase lipids and liver enzymes like clozapine did. Olanzapine at 50 mg/day may be associated with more anticholinergic effects and weight gain than clozapine.", "The aim of this study was to compare in vivo striatal D2 dopamine receptor occupancy induced by olanzapine and haloperidol in schizophrenic patients using a baseline-endpoint [(123)I]IBZM single photon computed emission tomography (SPECT) design. The relationships of striatal D2 receptor occupancy with clinical efficacy and extrapyramidal symptoms (EPS) were also assessed. Twenty-seven inpatients with schizophrenia or schizophreniform disorder were included in a 4-week prospective, randomized, double-blind, parallel and comparative clinical trial. Thirteen patients were treated with haloperidol (10 mg/day) and 14 with olanzapine (10 mg/day). Ratings of clinical status and EPS were obtained weekly. The percentage of D2 receptor occupancy was estimated by using basal ganglia (striatum)/frontal cortex IBZM uptake ratios obtained from each patient before and after 4 weeks of maintained antipsychotic treatment. Olanzapine led to a mean striatal D2 receptor occupancy of 49% (range 28-69%), which was significantly lower than that induced by haloperidol (mean 64%, range 46-90%). The baseline-endpoint SPECT design used in this study revealed lower antipsychotic D2 occupancy percentage values than those reported in the literature, using other approaches. The degree of striatal D2 receptor occupancy correlated to the EPS, which predominantly appeared in patients on haloperidol. No relationship was found between the striatal D2 receptor occupancy and clinical improvement. Olanzapine induced a lower striatal D2 occupancy than haloperidol. This low striatal D2 occupancy, together with the lower incidence of EPS in olanzapine-treated patients, contributed to confirm the atypical behavior of this new antipsychotic drug. Nevertheless, conclusions based on SPECT-estimated percentages of antipsychotic D2 occupancy should be cautious, since the SPECT design could influence the results. In this regard, SPECT studies including baseline and endpoint examinations should be encouraged." ]

[ "9832348", "21869697", "9413414", "11579351", "11147927", "17196045", "11074227", "16160624", "8263318" ]

[ "Double-blind, multicenter comparative study of sertraline and amitriptyline in hospitalized patients with major depression.", "Faster onset of antidepressant effects of citalopram compared with sertraline in drug-naïve first-episode major depressive disorder in a Chinese population: a 6-week double-blind, randomized comparative study.", "A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression.", "Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction.", "Double-blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression.", "A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder.", "Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline.", "Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial.", "Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression." ]

[ "Sertraline is a selective serotonin reuptake inhibitor (SSRI) for which marketing approval has been obtained recently in Germany. The results of several double-blind, placebo-controlled studies have demonstrated that sertraline has a clear antidepressive effect. However these studies have been conducted in outpatient populations. In the context of this multicenter study, a total of 160 inpatients were treated with sertraline 50-150 mg or amitriptyline 75-225 mg over a period of 6 weeks in a double-blind fashion. Sixty-two patients in the sertraline and 59 patients in the amitriptyline group were evaluated for efficacy in the according-to-protocol (ATP) population; 80 sertraline and 75 amitriptyline patients were evaluated for safety in the Intention-to-treat population (ITT). No statistically significant differences were detected between the two groups in the efficacy analysis performed on the basis of the Hamilton Depression Scale (HAM-D) total score and Clinical Global Impression (CGI). Due to its sedating properties, amitriptyline was found to be significantly more effective with regard to the HAM-D factor \"sleep disturbance\". The safety analysis, which was based on the CGI, the global assessment at the end of study and a score for somatic adverse events (FSUCL) revealed statistically significant advantages of sertraline over amitriptyline. Amitriptyline was associated with more autonomic and circulatory side effects, while epigastric complaints occurred more often with sertraline. The incidence of nausea - a typical SSRI side effect - was the same in both groups.", "Several previous studies, including a meta-analysis, reported no significant differences between various selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder. However, because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups, a head-to-head comparative study between SSRIs in different populations may be enlightening. We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded randomized clinical trial in a Chinese population of drug-naïve patients with first-episode major depressive disorder. Fifty-one patients were randomly assigned to citalopram or sertraline treatment. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary outcome. Efficacy and adverse effects were analyzed in an intent-to-treat population. Efficacy was analyzed using a last-observation-carried-forward method for early terminators. There were no significant differences in demographic characteristics at baseline. No significant differences were found in MADRS scores between citalopram and sertraline at baseline (36.6 ± 5.5 vs 38.2 ± 4.9; P = 0.322) or at the end of treatment (week 6; 10.8 ± 10.0 vs 16.7 ± 11.3; P = 0.082). However, MADRS scores in the citalopram group were significantly lower at week 1 (25.2 ± 8.5 vs 30.4 ± 6.1; P = 0.029) and week 3 (15.9 ± 10.0 vs 22.1 ± 8.7; P = 0.037). Overall, treatment-emergent adverse effects were reported by 14.3% and 28.6% of patients in the citalopram and sertraline groups, respectively. In conclusion, citalopram and sertraline were both efficacious and well tolerated. However, citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment, although the statistic was not significant.", "This study was designed to compare the efficacy, safety, tolerability profiles, and effects on quality of life of the serotonin selective reuptake inhibitor antidepressant sertraline versus the nonselective tricyclic antidepressant amitriptyline and placebo in patients with major depression.\n Outpatients with DSM-III-R major depression were randomly assigned to double-blind treatment for 8 weeks with sertraline (50-200 mg daily), amitriptyline (50-150 mg daily), or matching placebo. Assessments included the Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness scale, Clinical Global Impressions-Improvement scale, Global Assessment Scale, Profile of Mood States, Beck Depression Inventory, Quality of Life Enjoyment and Satisfaction Questionnaire, and Health-Related Quality of Life battery.\n All treatment groups demonstrated statistically significant improvement from baseline in depression ratings by Week 1 and thereafter. The antidepressant effects of amitriptyline and sertraline were significantly (p < .05) greater than placebo and did not differ significantly from each other. Sertraline was associated with significantly (p < .05) greater subjective (i.e., patient-rated) improvement in mood than amitriptyline or placebo. Both active drugs were associated with greater improvements than placebo on most quality of life measurements. On several items, sertraline, but not amitriptyline, was superior to placebo. There was a discernible effect of sertraline earlier than amitriptyline on most quality of life scales. Amitriptyline therapy was associated with significantly more treatment-related adverse events, and discontinuations due to treatment-related adverse events, in comparison to both sertraline and placebo therapy.\n Sertraline and amitriptyline each were effective treatments for major depression as assessed by both physician- and patient-rated scales. These results show that sertraline therapy is better tolerated than amitriptyline therapy. Quality of life was also improved by effective antidepressant treatment, with sertraline showing a tendency to produce greater improvements on quality of life measures.", "Brain serotonin is known to possess sympathoinhibitory properties. The aim of this clinical physiologic study was to determine whether sertraline, a selective serotonin reuptake inhibitor, facilitates the rate of recovery of cardiac autonomic function after an acute myocardial infarction (MI) in patients with depression.\n Thirty-eight post-MI depressed patients were randomized to receive either sertraline 50 mg per day or placebo for 6 months. Depression was defined as a score >15 on the standardized Inventory to Diagnose Depression questionnaire taken at prehospital discharge and again within 2 weeks of the acute infarct. Eleven stable post-MI nondepressed patients served as a nonrandomized reference group during follow-up. Twenty-seven patients completed the randomization. All 3 groups were followed up closely in a multidisciplinary post-MI clinic where they underwent serial testing for both time and frequency domain heart rate variability (HRV) indices at baseline (1-2 weeks after MI) and at 6, 10, 14, 18, and 22 weeks. The rate of recovery of HRV was determined by use of a growth curve model based on repeated-measures analysis of variance. There was a linear rate of increase in the SD of 24-hour N-N intervals (SDNN) in the sertraline-treated group that paralleled that of the nondepressed reference group. This contrasted with a modest but significant decline in SDNN in the placebo group from 2 to 22 weeks (t = 2.10, P <.05). However, the short-term power spectral indices, while trending toward a more rapid rate of recovery in the treated group, did not reach statistical significance compared with the placebo group.\n In depressed patients who have survived the acute phase of an MI sertraline facilitates the rate of recovery of SDNN, a recognized predictor of clinical outcome.", "To compare the efficacy and safety of sertraline and amitriptyline in a German outpatient population.\n Patients with Major Depression (DSM-III-R) and HAM-D (21 items) > or = 21 in 19 German centers received double-blind treatment with sertraline (initial dose 50 mg, titration up to 100 mg) or amitriptyline (75 mg, up to 150 mg) over 6 weeks. HAM-D (21 items), HAM-D Bech, CGI, DSI and SDS were evaluated for the efficacy analysis. FSUCL (Fischer Somatic and Undesired Effects Check List) and spontaneously reported adverse events were used for safety analysis.\n Of the 240 patients enrolled in the study, 205 (100 sertraline; 105 amitriptyline) were evaluable for efficacy. No statistically significant differences were detected between the two groups in the ITT and ATP efficacy analyses. Response, defined as score 1 (very much improved) or 2 (much improved) of the CGI improvement score, was 76% in the sertraline and 81% in the amitriptyline group (efficacy evaluable patients = ATP population). In the structured FSUCL, the side-effect burden (FSUCL score >2 for drug related symptoms) was significantly higher in the amitriptyline group at all follow up visits (p<0.05).\n Both sertraline and amitriptyline are suitable for the treatment of Major Depression; sertraline is comparable to amitriptyline with regard to efficacy, and offers the additional benefit of a more favorable safety profile.", "Sertraline may produce dual neurotransmitter effects similar to the serotonin-norepinephrine reuptake inhibitors (SNRIs); however, it has been tested against an SNRI in only 1 previous study, and never at an optimal dose. The objective of the current multisite study was to compare relatively higher doses of sertraline (i.e., 150 mg/day) and venlafaxine extended release (XR) (225 mg/day) in outpatients with major depressive disorder.\n Subjects with DSM-IV major depressive disorder were randomly assigned to 8 weeks of double-blind treatment with sertraline (N = 82) or venlafaxine XR (N = 78). The study ran from January 2002 through January 2003. The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Questionnaire; secondary outcome variables included the 17-item Hamilton Rating Scale for Depression.\n Both treatments led to significant improvement in depressive symptoms and quality-of-life measures. No significant differences were noted between treatment groups for final scores on the primary or secondary measures. The treatment groups did not differ significantly in the percentage of responders (sertraline = 55%, venlafaxine XR = 65%; intent-to-treat [ITT] sample) or remitters (sertra-line = 38%, venlafaxine XR = 49%; ITT sample), although the proportions are similar to those found in earlier selective serotonin reuptake inhibitor (SSRI) vs. venlafaxine meta-analyses. In patients who achieved the maximum dose of drug and maintained it for 3 weeks, response rates were similar to those found at lower doses (sertraline = 59%, venlafaxine XR = 70%); however, remission rates for this sample were comparable for both drug groups (sertraline = 48%, venlafaxine XR = 50%).\n The efficacies of sertraline and venlafaxine XR were comparable. Although response and remission rates did not differ statistically, the rates were analogous to those reported in previous meta-analyses. However, at clinically relevant higher doses, the remission rates were very similar.\n ClinicalTrials.gov identifier NCT00179283.", "Previous comparative studies of the selective serotonin reuptake inhibitors (SSRIs) have rarely included a placebo control group and have rarely demonstrated significant between-group differences. The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs, citalopram and sertraline.\n Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were randomized to 24 weeks of double-blind treatment with citalopram (20-60 mg/day), sertraline (50-150 mg/day), or a placebo. The primary efficacy measure was the Hamilton Depression Rating Scale (HAMD) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group.\n Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impression Scale. Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group; however, sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation, and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments. The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram, but not sertraline, relative to placebo.\n This study confirms the antidepressant efficacy of two SSRIs, citalopram and sertraline. It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy.", "Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients.\n Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below.\n At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs.\n The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies.", "An eight-week double-blind, multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression (DSM-III-R). There were 108 out-patients, from nine Italian centres, entered into the study, of whom 88 were evaluable (48 sertraline, 40 fluoxetine). The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg. Both treatment groups showed a statistically significant improvement from baseline at one week, and this was maintained until the end of treatment for all of the following measures: Hamilton Rating Scales for Depression and Anxiety, the Montgomery Asberg Depression Rating Scale, Clinical Global Impressions Scale, Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Questionnaire. Although there was a numerical advantage for sertraline on several efficacy measures, there was no statistically significant difference found between the treatment groups. The incidence of adverse events was similar for both treatments; 40.4% for sertraline and 39.3% for fluoxetine. However, adverse events were generally rated by patients as of lower severity in the sertraline group. In addition, for the fluoxetine group, there was a higher incidence of agitation, anxiety and insomnia than for sertraline. Sertraline was considered to be better tolerated than fluoxetine overall, since only 9.6% of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6%. By contrast, 13.5% of sertraline-treated patients discontinued prematurely because of clinical improvement, compared with 10.7% of fluoxetine-treated patients." ]

[ "7815243", "8675168", "8201224", "1505913", "3527321", "14687046", "8855091", "8975951", "16285948" ]

[ "Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial.", "Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis.", "Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period.", "Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial.", "A randomized clinical trial of oral ursodeoxycholic acid in obstructive jaundice.", "A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis.", "Ursodeoxycholic acid therapy in pregnant women with cholestasis.", "Ursodeoxycholic acid does not improve the clinical course of primary sclerosing cholangitis over a 2-year period.", "High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study." ]

[ "Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and, in an uncontrolled study, also in young adults with cystic fibrosis (CF) and chronic cholestasis. As an improvement in nutritional status was also observed in these young adult patients, we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease. The study included 51 patients (27 male patients and 24 female patients; age range, 8-32 years; median, 14) with body mass percentiles < 90%. Patients were randomly assigned to receive either ursodeoxycholic acid (10-12 mg/kg/day) alone or with taurine (18-22 mg/kg/day). Patients were followed in a crossover fashion within each group; 6 months of treatment was randomly alternated with 6 months of placebo. Nine patients dropped out before concluding the study. Liver function tests, nutritional status, and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment. Nutritional status and fat absorption were not significantly modified by either treatment. Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease. Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid, either alone or with taurine, does not improve the nutritional status of young malnourished CF patients. Higher doses given for longer periods might be worth investigating.", "Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis (CF). Preliminary data suggest that ursodeoxycholic acid (UDCA) may be beneficial for treatment of this manifestation. We performed a double-blind, multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA. From June to December 1990, we enrolled in 12 centers 55 CF patients with liver disease (39 male subjects; median age, 13.8 years). They were randomly assigned to receive for 1 year one of the following treatments: UDCA (15 mg/kg body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or double placebo. Clinical and laboratory evaluations were performed every 3 months. After 1 year, deterioration of overall clinical conditions, as indicated by the Shwachman-Kulczycki score (SKS), occurred in patients who received placebo but not in those who received UDCA (P = .025). Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase (GGT) (P = .004) and 5'-nucleotidase (P = .006) levels. Treatment with taurine was followed by a significant increase in serum prealbumin levels (P = .053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical profile. No severe side effects occurred with any treatment. Thus, we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease. Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status.", "Primary sclerosing cholangitis is a cholestatic disease of the liver characterized by progressive fibrotic inflammation and obliteration of the extra- and/or intrahepatic bile ducts. There is no effective therapy. We, therefore, studied the safety and efficacy of ursodeoxycholic acid in patients with primary sclerosing cholangitis with or without additional ulcerative colitis. In a 1-year ursodeoxycholic acid treatment period, which preceded the controlled study period, ursodeoxycholic acid was well tolerated in 22 of 24 patients with ulcerative colitis and in all three patients without ulcerative colitis. In two patients with ulcerative colitis the dose of 750 mg ursodeoxycholic acid/day led to diarrhea, but following reduction of the dose to 500 and 250 mg/day ursodeoxycholic acid was well tolerated. After 1 year of ursodeoxycholic acid treatment, 20 patients were randomly assigned to receive either ursodeoxycholic acid 750 mg/day or placebo. All of them finished a double-blind, placebo-controlled study period. During ursodeoxycholic acid treatment, the liver enzymes improved markedly. The difference in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyltransferase between the placebo and ursodeoxycholic acid group was significant (p < 0.05). Following ursodeoxycholic acid treatment, pruritus and fatigue improved in half of the patients but the difference between the placebo and ursodeoxycholic acid group was not significant. According to the ethical guidelines, after 3 months of placebo treatment, the controlled study had to be discontinued because of a more than twofold increase of serum transaminases in 8/10 patients on placebo. After the end of the controlled study, all patients were continuously treated with ursodeoxycholic acid for up to 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)", "The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver histological appearance and endoscopic retrograde cholangiography were included in the trial. Six patients received ursodeoxycholic acid (13 to 15 mg/kg body wt/day), and eight patients received placebo. Two patients had to be withdrawn from the study, one because of UDCA-related diarrhea and the other because of worsening of the disease during placebo treatment. Patients in the ursodeoxycholic acid group improved significantly during 1 yr of treatment with respect to serum levels of bilirubin (median = -50%), alkaline phosphatase (median = -67%), gamma-glutamyltransferase (median = -53%), AST (median = -54%) and ALT (median = -36%) compared with the placebo group, but not with respect to serum levels of hydrophobic bile acids. During ursodeoxycholic acid treatment, histopathological features also improved significantly, as evaluated by multiparametric score. Expression of human leukocyte antigen class I molecules appeared to be markedly reduced on liver cells after ursodeoxycholic acid treatment. We conclude that ursodeoxycholic acid is beneficial in reducing disease activity in patients with primary sclerosing cholangitis.", "Forty patients with obstructive jaundice (bilirubin greater than 100 mumol/l) were entered into a randomized trial of oral ursodeoxycholic acid for 48 h before surgery versus no additional therapy. Pre-operative venous and operative portal total bile salt concentrations were higher in the bile salt treated patients (P less than 0.001). Portal endotoxaemia during operation was reduced in ursodeoxycholic acid treated patients (P less than 0.05). There was no significant difference in systemic venous endotoxaemia, renal function or postoperative morbidity or mortality. This study suggests pre-operative oral bile salt therapy may be of no clinical benefit in patients with obstructive jaundice.", "To compare the efficacy of S-adenosyl-l-methionine and ursodeoxycholic acid in improving serum biochemical abnormalities in gestational cholestasis.\n Randomised clinical trial.\n University hospital.\n All women at <36 weeks of gestation with severe gestational cholestasis during June 1996 to December 2001.\n Enrolled women were randomly assigned oral S-adenosyl-l-methionine 500 mg twice daily or oral ursodeoxycholic acid 300 mg twice daily until delivery.\n Reduction in the concentration of serum bile acids. Other variables considered included obstetric and neonatal outcome, clinical symptoms and other laboratory measurements (serum levels of transaminases and bilirubin). The two groups were compared using Student's t test, Wilcoxon's signed rank sum test and Fisher's exact test, with a two-tailed P < 0.05 being considered significant.\n Of the 46 women enrolled, 24 received ursodeoxycholic acid and 22 S-adenosyl-l-methionine. At enrolment, gestational age, duration of therapy, rate of nulliparity, pruritus score and biochemical characteristics were similar between the groups. Both therapies significantly and equally improved pruritus. Women receiving ursodeoxycholic acid had a significantly greater improvement in the concentration of serum bile acids (P= 0.001), aspartate aminotransferase (P= 0.01), alanine aminotransferase (<0.001) and bilirubin (P= 0.002) compared with those receiving S-adenosyl-l-methionine. Duration of therapy was significantly greater in women receiving ursodeoxycholic acid compared with S-adenosyl-l-methionine (P= 0.04), whereas gestational age at delivery and rate of prematurity were similar in the two groups.\n In women with intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is more effective than S-adenosyl-l-methionine at improving the concentration of serum bile acids and other tests of liver function, whereas both therapies are equally effective at improving pruritus.", "To test the efficacy and safety of ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy (ICP) by a randomized, double-blind, placebo-controlled trial.\n Eight patients with pruritus and abnormal liver function tests received 600 mg/day of UDCA in two doses for 20 days, compared with a control group of eight patients who received placebo for 20 days.\n No adverse reactions were detected in any patient. During UDCA therapy a statistically significant improvement in pruritus, serum bile salt levels, serum glutamic pyruvic transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase and total and direct bilirubin was observed. Only two patients treated with UDCA underwent cesarean sections due to reasons unrelated to the therapeutic trial. All newborns had an Apgar score >7 and normal postnatal growth.\n Although the number of patients in this study was very small, we suggest that UDCA treatment has a role in improving clinical and biochemical results in ICP.", "Ursodeoxycholic acid has been shown to be a useful agent in the clinical management of patients with primary biliary cirrhosis and autoimmune chronic active hepatitis. Its efficacy is presumed to be based upon its ability to act as a detergent and to incite a choleresis. Recent additional data suggest it also reduces HLA antigen expression on liver and biliary epithelial cells and impairs T cell reactivity.\n A randomized controlled study of 59 patients with primary sclerosing cholangitis was performed over a 24 months period with 3 groups being studied. Group I consisted of 20 patients who were given ursodeoxycholic acid 300 mg orally twice a day; group II consisted of 19 patients who were given colchicine 0.6 mg orally BID; and group III was an untreated medical control group. All three groups were seen at regular 3-month intervals and had quarterly, annual and terminal studies performed to assess their disease status.\n No difference between groups was evident after two full years of therapy when parameters of liver injury, liver function, liver size and hepatic copper content were compared between groups. Similarly, no difference in ERCP findings was evident between groups either at entry or after two years of therapy.\n These data suggest that ursodeoxycholic acid is no better than colchicine or simple medical follow-up. Thus, neither ursodeoxycholic acid or colchicine can be considered to be effective therapies for primary sclerosing cholangitis.", "There is no medical treatment of proven benefit for primary sclerosing cholangitis. This study aimed at studying the effect of a higher dose of ursodeoxycholic acid than previously used on survival, symptoms, biochemistry, and quality of life in this disease.\n A randomized placebo-controlled study was performed in tertiary and secondary gastroenterology units. A total of 219 patients were randomized to 17 to 23 mg/kg body weight per day of ursodeoxycholic acid (n = 110) or placebo (n = 109) for 5 years. Follow-up data are available from 97 patients randomized to ursodeoxycholic acid and for 101 randomized to placebo. Quality of life was assessed by using the Medical Outcomes Study 36-item Short-Form Health Survey.\n The combined end point \"death or liver transplantation\" occurred in 7 of 97 (7.2%) patients in the ursodeoxycholic acid group vs 11 of 101 (10.9%) patients in the placebo group (P = .368; 95% confidence interval, -12.2% to 4.7%). The occurrence of liver transplantation as a single end point showed a similar positive trend for ursodeoxycholic acid treatment (5/97 [5.2%] vs 8/101 [7.9%]; 95% confidence interval, -10.4% to 4.6%). Three ursodeoxycholic acid and 4 placebo patients died from cholangiocarcinoma, and 1 placebo patient died from liver failure. Alkaline phosphatase and alanine aminotransferase tended to decrease during the first 6 months. There were no differences between the 2 groups in symptoms or quality of life. Analyses of serum ursodeoxycholic acid concentration gave no evidence that noncompliance may have influenced the results.\n This study found no statistically significant beneficial effect of a higher dose of ursodeoxycholic acid than previously used on survival or prevention of cholangiocarcinoma in primary sclerosing cholangitis." ]

[ "16137357", "8951252", "10051081", "8120720", "9255192", "11098980", "12441749", "17133185", "16572737" ]

[ "High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669].", "The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.", "A prospective randomized comparison of conventional mechanical ventilation and very early high frequency oscillatory ventilation in extremely premature newborns with respiratory distress syndrome.", "Prospective, randomized comparison of high-frequency oscillation and conventional ventilation in candidates for extracorporeal membrane oxygenation.", "Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn.", "Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn.", "Interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in pediatrics.", "High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation.", "Plasma soluble intercellular adhesion molecule-1 (sICAM-1) in pediatric ARDS during high frequency oscillatory ventilation: a predictor of mortality." ]

[ "To compare the safety and efficacy of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CV) for early intervention in adult respiratory distress syndrome (ARDS), a multi-centre randomized trial in four intensive care units was conducted.\n Patients with ARDS were randomized to receive either HFOV or CV. In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures. CV ventilation strategy was aimed at reducing tidal volumes. In the HFOV group, an open lung strategy was used. Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up.\n The study was prematurely stopped. Thirty-seven patients received HFOV and 24 patients CV (average APACHE II score 21 and 20, oxygenation index 25 and 18 and duration of mechanical ventilation prior to randomization 2.1 and 1.5 days, respectively). There were no statistically significant differences in survival without supplemental oxygen or on ventilator, mortality, therapy failure, or crossover. Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 (95% CI 0.22-2.97) for survival without oxygen or on ventilator, and an odds ratio for mortality of 1.15 (95% CI 0.43-3.10) for HFOV compared with CV. The response of the oxygenation index (OI) to treatment did not differentiate between survival and death. In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day. A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI.\n No significant differences were observed, but this trial only had power to detect major differences in survival without oxygen or on ventilator. In patients with ARDS and higher baseline OI, however, there might be a treatment benefit of HFOV over CV. More research is needed to establish the efficacy of HFOV in the treatment of ARDS. We suggest that future studies are designed to allow for informative analysis in patients with higher OI.", "To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support.\n A prospective randomized clinical trial.\n Three community-based level III neonatal intensive care units.\n A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50.\n Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit.\n No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants.\n When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.", "To compare the effectiveness and safety of very early high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) in treatment of the respiratory distress syndrome (RDS) and to evaluate their impact on the incidence of chronic pulmonary disease and early and late morbidity of very low-birthweight neonates.\n A prospective randomized clinical trial.\n Tertiary neonatal intensive care unit in the Perinatology Center in Prague.\n 43 premature newborns, delivered in the Department of Obstetrics in the Perinatology Center, were randomly divided into two groups (HFOV and CMV) immediately after delivery; 2 patients in each group died, 2 fulfilled crossover criteria from CMV to HFOV, and 2 were excluded because of congenital malformations. Nineteen patients treated with HFOV were therefore compared with 18 infants in the CMV group.\n The two contrasting modes of ventilation were introduced immediately after intubation. Maintenance of optimal lung volume in HFOV to optimize oxygenation and the therapeutic administration of surfactant after fulfilling defined criteria are important points of the strategy and design of the study.\n Except for a higher proportion of males in the HFOV group (p<0.02), the basic clinical characteristics (gestational age, birthweight, Apgar score at 5 min, umbilical arterial pH), the two groups were similar. In the acute stage of RDS, infants treated with HFOV had higher proximal airway distending pressure with HFOV for 6 h after delivery (p<0.05). For a period of 12 h after delivery lower values for the alveolar-arterial oxygen difference (p<0.03) were noted. The number of patients who did not require surfactant treatment was higher in the HFOV group (11 vs. 1, p<0.001). In the HFOV group the authors found a lower roentgenographic score at 30 days of age (p<0.03) and a lower clinical score in the 36th postconceptional week (p<0.05), using these two scoring systems for assessing chronic lung disease according to Toce scale. The incidence of pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage and retinopathy of prematurity in both groups was the same.\n HFOV, when applied early and when the clinical strategy of maintenance of optimal lung volume is used, improves oxygenation in the acute stage of RDS, reduces the need of surfactant administration, and can decrease the injury to lung tissue even in extremely immature newborns to whom surfactant is administered therapeutically.", "To compare the safety and efficacy of high-frequency oscillation (HFO) with conventional ventilation in the treatment of neonates with respiratory failure.\n We conducted a multicenter, prospective, randomized trial. Patients were stratified according to pulmonary diagnosis and then were randomly selected for conventional ventilation or HFO. A balanced crossover design offered patients who met criteria of treatment failure a trial of the alternative mode of ventilation.\n Four tertiary, level 3 neonatal intensive care units accepting regional referrals for extracorporeal membrane oxygenation.\n Neonates were eligible for enrollment if their gestational age was > 34 weeks, their birth weight was > or = 2 kg, they were < 14 days of age, they required fractional inspired oxygen > 0.50 and a mean airway pressure > 0.98 kPa (10 cm H2O) to support adequate oxygenation, and they required a peak inspiratory pressure > 2.9 kPa (30 cm H2O) and a rate > 40 breaths per minute to support adequate ventilation. Exclusion criteria were lethal congenital anomalies, profound shock, need for cardiopulmonary resuscitation, and failure to obtain consent.\n Of 79 patients studied, 40 were assigned to conventional ventilation and 39 to HFO. Neonates randomly assigned to HFO required higher peak pressure (3.8 +/- 0.5 vs 3.3 +/- 0.8 kPa, 39 +/- 5 vs 34 +/- 8 cm H2O; p = 0.004) and more often met extracorporeal membrane oxygenation criteria (67% vs 40%; p = 0.03) at study entry than did those given conventional ventilation. Twenty-four patients (60%) assigned to conventional ventilation met treatment failure criteria compared with 17 (44%) of those assigned to HFO (not significant). Of the 24 patients in whom conventional ventilation failed, 15 (63%) responded to HFO; 4 (23%) of the 17 in whom HFO failed responded to conventional ventilation (p = 0.03). There were no differences between the two groups with respect to outcome, need for extracorporeal membrane oxygenation, or complications.\n We conclude that HFO is a safe and effective rescue technique in the treatment of neonates with respiratory failure in whom conventional ventilation fails.", "Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed.\n To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (n = 70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) (\"other\": n = 43), and congenital diaphragmatic hernia (n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained PaO2 of 60 mm Hg or greater.\n Baseline oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (p < 0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%).\n We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN.", "We previously reported improved oxygenation, but no change, in rates of extracorporeal membrane oxygenation (ECMO) use or death among infants with persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (NO) with conventional ventilation, irrespective of lung disease. The goal of our study was to determine whether treatment with inhaled NO improves oxygenation and clinical outcomes in infants with persistent pulmonary hypertension of the newborn and associated lung disease who are ventilated with high-frequency oscillatory ventilation (HFOV).\n Single-center, prospective, randomized, controlled trial.\n Newborn intensive care unit of a tertiary care teaching hospital.\n We studied infants with a gestational age of > or =34 wks who were receiving mechanical ventilatory support and had echocardiographic and clinical evidence of pulmonary hypertension and hypoxemia (PaO2 < or =100 mm Hg on FIO2 = 1.0), despite optimal medical management Infants with congenital heart disease, diaphragmatic hernia, or other major anomalies were excluded.\n The treatment group received inhaled NO, whereas the control group did not. Adjunct therapies and ECMO criteria were the same in the two groups of patients. Investigators and clinicians were not masked as to treatment assignment, and no crossover of patients was permitted.\n Primary outcome variables were mortality and use of ECMO. Secondary outcomes included change in oxygenation and duration of mechanical ventilatory support and supplemental oxygen therapy. Forty-two patients were enrolled. Baseline oxygenation and clinical characteristics were similar in the two groups of patients. Infants in the inhaled NO group (n = 21) had improved measures of oxygenation at 15 mins and 1 hr after enrollment compared with infants in the control group (n = 20). Fewer infants in the inhaled NO group compared with the control group were treated with ECMO (14% vs. 55%, respectively; p = .007). Mortality did not differ with treatment assignment.\n Among infants ventilated by HFOV, those receiving inhaled NO had a reduced need for ECMO. We speculate that HFOV enhances the effectiveness of inhaled NO treatment in infants with persistent pulmonary hypertension of the newborn and associated lung disease.", "High-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) have been reported to improve oxygenation in children with acute hypoxemic respiratory failure (AHRF), but their roles in the treatment of AHRF remains unknown. The use of HFOV improves oxygenation by increasing lung recruitment. iNO can improve oxygenation in AHRF, but it may have limited efficacy in patients with poor lung inflation. Based on these findings, we hypothesized that the combined treatment of HFOV and inhalation of low-dose NO would improve oxygenation and survival in children with severe AHRF compared with children treated with conventional mechanical ventilation (CMV) or either treatment alone.\n Tertiary pediatric intensive care units at seven academic centers.\n Post hoc analysis of data from children enrolled in a multicenter, randomized, masked study of the use of iNO in the treatment of AHRF.\n A total of 108 pediatric patients with AHRF defined as an oxygenation index of >15 twice within 6 hrs. Mode of ventilation (HFOV or CMV) was determined by the patient's physician based on guidelines to maximize oxygenation. The patient was then randomized to treatment with or without iNO. Comparisons were made between patients who were treated with HFOV plus iNO (n = 14), HFOV alone (n = 12), CMV plus iNO (n = 35), and CMV alone (n = 38).\n Ventilation with CMV or HFOV with or without iNO.\n We found that the change in Pao /Fio ratio was greatest in the HFOV plus iNO group compared with the other treatment groups at 4 hrs (p =.02) and 12 hrs (p =.01). After 24 hrs of treatment, both HFOV plus iNO and HFOV alone resulted in greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.005). After 72 hrs, treatment with HFOV alone resulted in a greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.03). There was no difference in predefined treatment failures between treatment groups.\n We conclude that the combination of HFOV with iNO causes a greater improvement in oxygenation than either treatment strategy alone in children with severe AHRF. We speculate that the enhanced lung recruitment by HFOV enhances the effects of low dose iNO on gas exchange.", "The improvement in oxygenation with prone positioning is not persistent when patients with acute respiratory distress syndrome (ARDS) are turned supine. High-frequency oscillatory ventilation (HFOV) aims to maintain an open lung volume by the application of a constant mean airway pressure. The aim of this study was to show that HFOV is able to prevent the impairment in oxygenation when ARDS patients are turned back from the prone to the supine position.\n Prospective, comparative randomized study.\n A medical intensive care unit.\n Forty-three ARDS patients with a Pao2/Fio2 ratio <150 at positive end-expiratory pressure > or =5 cm H2O.\n After an optimization period, the patients were assigned to one of three groups: a) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by a 12-hr period of conventional lung-protective mechanical ventilation in the supine position (CV(prone)-CV(supine)); b) conventional lung-protective mechanical ventilation in the supine position (12 hrs) followed by HFOV in the supine position (12 hrs) (CV(supine)-HFOV(supine)); or c) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by HFOV in the supine position (CV(prone)-HFOV(supine) group).\n Pao2/Fio2 ratio was higher at the end of the study period in the CV(prone)-HFOV(supine) group than in the CV(prone)-CV(supine) group (p < .02). Venous admixture at the end of the study period was lower in the CV(prone)-HFOV(supine) group than in the two other groups.\n HFOV maintained the improvement in oxygenation related to prone positioning when ARDS patients were returned to the supine position.", "Soluble intercellular adhesion molecule-1 (sICAM-1), an important adhesion molecule that mediates leukocyte-endothelial interaction, has been identified as a marker for the outcome of acute respiratory tract infection. We postulate that plasma ICAM-1 may be a valuable marker for both biological and clinical severity of acute respiratory distress syndrome (ARDS). Sixteen pediatric patients (> 1 month and < 15 years of age) diagnosed with ARDS were recruited from the Pediatric Intensive Care Unit at King Chulalongkorn Memorial University Hospital, Bangkok. The patients were randomized to receive either high frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation. Plasma sICAM-1 was measured by enzyme linked immunosorbent assay (ELISA) on days 1, 3, 5 and 7 of ARDS. Plasma sICAM-1 levels in survivors and non-survivors of the HFOV and conventional treatment groups were compared. Nine and 7 patients constituted the control group receiving conventional treatment and HFOV group, respectively. Overall nine patients survived. The patients in the HFOV group had a better chance of survival compared to the controls (71% versus 31.5%), but it was not statistically significant (p = 0.2). The overall mortality was 45.7%. The mean plasma sICAM-1 levels (n = 13/16) were significantly elevated among non-survival patients as compared to survival patients at all time points, which indicates that an unfavorable outcome in ARDS is related to the degree of epithelial and endothelial alveolar cell injury. The elevation of plasma slCAM-1 on day 3 provided the best predictor of mortality (likelihood ratio 11.9, p < 0.001). It was concluded that HFOV facilitated a potentially better outcome compared to conventional treatment and it was associated with less lung injuries evidenced by lower plasma sICAM-1." ]

[ "17768579", "19144672", "18392378", "6610435", "3306163", "12595838", "10807441", "15077078", "10807440" ]

[ "Prevention of atrial fibrillation with moderate doses of amiodarone in the postoperative period of cardiac surgery is safe and effective in patients with high risk for developing this arrhythmia.", "Prevention of atrial fibrillation after coronary artery bypass grafting via atrial electromechanical interval and use of amiodarone prophylaxis.", "Influence of external temporary biatrial pacing on the prevention of atrial fibrillation after coronary artery bypass without extracorporeal circulation.", "Arrhythmias after coronary bypass surgery.", "Predictors, prevention, and long-term prognosis of atrial fibrillation after coronary artery bypass graft operations.", "Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: the beta-Blocker Length Of Stay (BLOS) study.", "Atrial pacing for the prevention of atrial fibrillation after cardiovascular surgery.", "A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial.", "Effective prevention of atrial fibrillation by continuous atrial overdrive pacing after coronary artery bypass surgery." ]

[ "To assess if prophylaxis with moderate doses of amiodarone in the postoperative period of cardiac surgery (coronary artery bypass grafting and/or valve surgery), reduces the incidence of atrial fibrillation in patients with high risk for developing this arrhythmia.\n A randomized and prospective clinical study involving 68 patients who underwent elective cardiac surgery. Mean age was 64 years and 59% of participants were males. Patients with three or more risk factors for atrial fibrillation, according to the literature, were randomized into two groups to receive or not prophylaxis with amiodarone in the first postoperative day. The dose administered ranged from 600 mg/day to 900 mg/day, intravenously, on the first postoperative day, followed by 400 mg/day orally until hospital discharge or until completing seven days. The other patients, who presented two or fewer risk factors, were followed up until hospital discharge. All patients were evaluated by means of cardiac and/or electrocardiographic monitoring.\n In the group treated with amiodarone, 7% of patients presented atrial fibrillation, whereas in the control group 70% of patients developed arrhythmia. Among the non-randomized individuals (with two or fewer risk factors), only 24% presented atrial fibrillation.\n The prophylactic use of amiodarone was effective in the prevention of atrial fibrillation in patients with three or more risk factors for this arrhythmia. This treatment can be useful to reduce stay at the Intensive Care Unit and, consequently, the complications originating from longer hospitalization.", "In our previous study, we defined a cut-off point of 120 ms for atrial electromechanical interval (AEMi) to determine the risk of atrial fibrillation (AF) occurrence. Accordingly, the present study sought to investigate whether or not a prophylactic perioperative administration of amiodarone could reduce the incidence of AF in a high-risk group (AEMi >120 ms) undergoing coronary artery bypass grafting (CABG). In this prospective, randomized study, 100 patients with AEMi >120 ms received either amiodarone (n=50) or placebo (n=50). The endpoints were AF occurrence after CABG and hospital and intensive care unit (ICU) lengths of stay after CABG. The incidence of postoperative AF was significantly higher in the placebo group than that of the amiodarone group (88% of patients in control group vs. 16% of patients in amiodarone group, P<0.0001). The prophylactic therapy with amiodarone significantly reduced the ICU length of stay (2.28+/-1.00 vs. 3.60+/-0.90 days, P<0.0001) and hospital length of stay (5.64+/-2.35 vs. 7.78+/-1.46 days, P<0.0001). The incidence of postoperative AF among patients with high AEMi was significantly reduced by a prophylactic amiodarone treatment, resulting in shorter ICU and hospital stays.", "Atrial fibrillation is the most common complication after myocardial revascularization, and it increases morbidity/mortality.\n The purpose of this prospective randomized study was to test the hypothesis that temporary biatrial pacing is effective in reducing the incidence of postoperative atrial fibrillation after myocardial revascularization.\n Ninety-eight non-consecutive patients who had undergone off-pump myocardial revascularization received two temporary electrodes attached to the right and left atria, which were connected to either pair of atrial pacemaker electrodes, in addition to the leads implanted in the right ventricle. Two groups of patients were randomized (control: 49 patients with no biatrial pacing; therapeutic: 49 patients with biatrial pacing). The variables of interest were atrial fibrillation (present or absent) and length of hospital stay.\n The incidence of atrial fibrillation was 36.73% in the control group and 14.29% in the therapeutic group (p=0.0194). Length of hospital stay was 7.00 +/- 2.82 days for patients with no atrial fibrillation (n=73) and 9.20 +/- 2.87 days for patients with atrial fibrillation (n=25) (p=0.0001). Age was an important predictor of arrhythmia and ranged between 62.34 +/- 9.00 years in the group with no atrial fibrillation and 67.20 +/- 7.42 years in the group with atrial fibrillation (p=0.0170).\n Compared to controls, prophylactic temporary biatrial pacing is effective in preventing atrial fibrillation. Hospital stay was longer for patients who developed postoperative atrial fibrillation, and age was an important predictor for the development of arrhythmia.", "Ninety patients undergoing coronary bypass surgery were studied prospectively by bedside and subsequent ambulatory electrocardiographic monitoring to investigate the incidence, possible causes, and prevention of atrial fibrillation. Patients with good left ventricular function were divided randomly into a control group or groups treated with digoxin or propranolol. In the control group the incidence of atrial fibrillation was 27% and of significant ventricular extrasystoles 3%. Propranolol reduced the incidence of atrial fibrillation (14.8%), whereas digoxin had no effect and increased the incidence of ventricular extrasystoles. Age, sex, severity of symptoms, cardiomegaly, heart failure, previous myocardial infarction, and number of grafts did not affect the result. The operative myocardial ischaemic time was related to the occurrence of atrial fibrillation. There was also a significant relation between atrial fibrillation and bundle branch block. Atrial fibrillation is common after coronary artery grafting; it may be due to diffuse myocardial ischaemia or hypothermic injury. The incidence may be reduced by beta blockade.", "Multiple trials have suggested the use of digoxin, digoxin and propranolol, or timolol to prevent atrial fibrillation after coronary artery bypass grafting. No trial has evaluated the efficacy of digoxin verus propranolol. Furthermore, the predictors of postoperative atrial fibrillation and the long-term consequence of atrial fibrillation that reverts to sinus rhythm have not been established. One hundred fifty patients were randomized to receive no drug, propranolol (20 mg every 6 hours), or digoxin (0.5 mg followed by 0.25 mg daily). Twenty-seven patients were excluded from data analysis. In the remaining 123 patients, no preoperative parameter (age, sex, diabetes, hypertension, smoking, electrocardiographic p wave morphology, or preoperative digoxin or propranolol therapy), intraoperative parameter (bypass time, aortic cross-clamp time, or number of vessels bypassed), or postoperative parameter (peak creatinine kinase, congestive heart failure, or pericarditis) by univariate or multivariate analysis predicted patients at risk for atrial fibrillation. Sustained atrial fibrillation developed in 37.5% of control and 32.6% of digoxin-treated patients. Only 16.2% of propranolol-treated patients had sustained atrial fibrillation (p less than 0.03). There were no in-hospital complications in those patients with atrial fibrillation. After 26 +/- 7 months follow-up, those patients with postoperative atrial fibrillation had no increased incidence of angina, cerebral vascular accident, myocardial infarction, or sudden death. Therefore, in this select population, propranolol prophylaxis is effective but discretionary.", "Atrial fibrillation (AF) is a common complication of heart surgery. Previous studies have shown that there is an association between postoperative AF and prolongation of hospital length of stay. No previous trials have been primarily directed at demonstrating that the use of drugs that prevent AF would shorten length of stay and reduce the costs of postoperative care.\n A randomized, double-blind, placebo-controlled trial of metoprolol was performed in patients immediately after nonemergent heart surgery. Metoprolol was given orally at a dose of 100 mg per day after the patient's arrival in the intensive care unit until hospital discharge or 14 days, whichever was sooner. This dose was increased to 150 mg per day after the enrollment of 411 patients. The primary outcome measure of the study was hospital length of stay from admission to intensive care unit until hospital discharge. There were 1000 patients enrolled, evenly distributed to the metoprolol and placebo groups.\n There was a 20% reduction in the risk of AF developing with metoprolol, from 39% of patients to 31% of patients (P =.01). There was no effect of treatment on hospital length of stay, which was 152 +/- 61 hours for placebo and 155 +/- 90 hours for metoprolol (P = 0.79). The cost of postoperative care in the 2 treatment groups was similar.\n Prophylactic metoprolol reduces the risk of AF after heart surgery. It does not reduce hospital length of stay. Although it is cost effective for the reduction of AF, it did not reduce the overall cost of care.", "The purpose of this study was to determine the efficacy of atrial pacing in the prevention of atrial fibrillation following cardiovascular surgery.\n Although pharmacologic therapy has been used to help prevent postoperative atrial fibrillation, it suffers from limited efficacy and adverse effects. In the nonoperative setting, novel pacing strategies have been shown to reduce recurrences of atrial fibrillation and prolong arrhythmia-free periods in patients with paroxysmal atrial arrhythmias.\n A total of 154 patients (115 men; mean age, 65 +/- 10 years; ejection fraction, 53 +/- 10%) undergoing cardiac surgery (coronary artery bypass surgery, 88.3%; aortic valve replacement, 4.5%; coronary bypass + aortic valve replacement, 7.1%) had right and left atrial epicardial pacing electrodes placed at the time of surgery. Patients were randomized to either no pacing, right atrial (RAP), left atrial (LAP) or biatrial pacing (BAP) for 72 h after surgery. Beta-adrenergic blocking agents were administered concurrently to all patients following surgery.\n There was a reduction in the incidence of postoperative atrial fibrillation from 37.5% in patients receiving no postoperative pacing to 17% (p < 0.005) in patients assigned to one of the three pacing strategies. The length of hospital stay was reduced by 22% from 7.8 +/- 3.7 days to 6.1 +/- 2.3 days (p = 0.003) in patients assigned to postoperative atrial pacing. The incidence of atrial fibrillation was lower in each of the paced groups (RAP, 8%; LAP, 20%; BAP, 26%) compared with patients who did not receive postoperative pacing (37.5%).\n Postoperative atrial pacing, in conjunction with beta-blockade, significantly reduced both the incidence of atrial fibrillation and the length of hospital stay following cardiovascular surgery. Additional studies are needed to determine the most effective anatomic pacing site.", "Atrial fibrillation (AF) frequently occurs after cardiac surgical procedures, and beta-blockers, sotalol, and amiodarone may reduce the frequency of AF after open heart surgery. This pilot trial was designed to test whether each of the active oral drug regimens is superior to placebo for prevention of postoperative AF and whether there are differences in favor of 1 of the preventive strategies.\n We conducted a randomized, double-blinded, placebo-controlled trial in which patients undergoing cardiac surgery in the absence of heart failure and without significant left ventricular dysfunction (n = 253; average age, 65 +/- 11 years) received oral amiodarone plus metoprolol (n = 63), metoprolol alone (n = 62), sotalol (n = 63), or placebo (n = 65). Patients receiving combination therapy (amiodarone plus metoprolol) and those receiving sotalol had a significantly lower frequency of AF (30.2% and 31.7%; absolute difference, 23.6% and 22.1%; odds ratios [OR], 0.37 [95% CI, 0.18 to 0.77, P <.01 vs placebo] and 0.40 [0.19 to 0.82, P =.01 vs placebo]) compared with patients receiving placebo (53.8%). Treatment with metoprolol was associated with a 13.5% absolute reduction of AF (P =.16; OR, 0.58 [0.29 to 1.17]. Treatment effects did not differ significantly between active drug groups. Adverse events including cerebrovascular accident, postoperative ventricular tachycardia, nausea, and dyspepsia, in hospital death, postoperative infections, and hypotension, were similar among the groups. Bradycardia necessitating dose reduction or drug withdrawal occurred in 3.1% (placebo), 3.2% (combined amiodarone and metoprolol; P =.65 vs placebo), 12.7% (sotalol; P <.05 vs placebo), and 16.1% (metoprolol; P <.05 vs placebo). Patients in the placebo group had a nonsignificantly longer length of hospital stay as compared with the active treatment groups (13.1 +/- 8.9 days vs 11.3 +/- 7; P =.10), with no significant difference between the active treatment groups.\n Oral active prophylaxis with either sotalol or amiodarone plus metoprolol may reduce the rate of AF after cardiac surgery in a population at high risk for postoperative AF. Treatment with metoprolol alone resulted in a trend to a lower risk for postoperative AF.", "The present study was aimed to evaluate the efficacy of a specific algorithm with continuous atrial dynamic overdrive pacing to prevent atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery.\n Atrial fibrillation occurs in 30% to 40% of patients after cardiac surgery with a peak incidence on the second day. It still represents a challenge for postoperative prevention and treatment and may have medical and cost implications.\n Ninety-six consecutive patients undergoing CABG for severe coronary artery disease and in sinus rhythm without antiarrhythmic therapy on the second postoperative day were randomized to have or not 24 h of atrial pacing through temporary epicardial wires using a permanent dynamic overdrive algorithm. Holter ECGs recorded the same day in both groups were analyzed to detect AF occurrence.\n No difference was observed in baseline data between the two study groups, particularly for age, male gender, history of AF, ventricular function, severity of coronary artery disease, preoperative beta-adrenergic blocking agent therapy or P-wave duration. The incidence of AF was significantly lower (p = 0.036) in the paced group (10%) compared with control subjects (27%). Multivariate analysis showed AF incidence to increase with age (p = 0.051) but not in patients with pacing (p = 0.078). It decreased with a better left ventricular ejection fraction only in conjunction with atrial pacing (p = 0.018).\n We conclude that continuous atrial pacing with an algorithm for dynamic overdrive reduces significantly incidence of AF the second day after CABG surgery, particularly in patients with preserved left ventricular function." ]

[ "17260365", "20049950", "19491859", "19891665", "15133864", "19766640", "20937044", "15342210", "15758622" ]

[ "Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis.", "Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study.", "Safety and efficacy of a new 3.3 g b.i.d. tablet formulation in patients with mild-to-moderately-active ulcerative colitis: a multicenter, randomized, double-blind, placebo-controlled study.", "Clinical trial: oral colon-release parnaparin sodium tablets (CB-01-05 MMX) for active left-sided ulcerative colitis.", "Different therapy for different types of ulcerative colitis in China.", "Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis.", "Clinical trial: once-daily mesalamine granules for maintenance of remission of ulcerative colitis - a 6-month placebo-controlled trial.", "An open-label, comparative study of the efficacy and safety of once-daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis.", "Topical treatment of distal active ulcerative colitis with beclomethasone dipropionate or mesalamine: a single-blind randomized controlled trial." ]

[ "In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies.\n We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events.\n Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred.\n In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC.", "Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC.\n In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI).\n In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles.\n Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288).", "To evaluate the safety and efficacy of a new twice-daily balsalazide disodium 1.1 g tablet dosing regimen (6.6 g/day, three tablets twice daily) for the treatment of mild-to-moderately-active ulcerative colitis (UC).\n In a double-blind, multicenter study patients with symptoms of acute UC and a baseline Modified Mayo Disease Activity Index (MMDAI) score between 6 and 10, inclusive, with a subscale rating of > or =2 for both rectal bleeding and mucosal appearance were randomized to receive 3.3 g of balsalazide or placebo tablets twice daily for 8 weeks. The primary end point was the proportion of patients achieving clinical improvement (> or =3 point improvement in MMDAI) and improvement in rectal bleeding (> or =1 point improvement) at 8 weeks. Safety assessments were conducted from baseline through 2-weeks post-treatment.\n A total of 249 patients (166 balsalazide, 83 placebo) received at least 1 dose of study medication. The mean MMDAI score at baseline was 7.9; 62% of patients had a score > or =8.0 (moderate disease). A significantly larger proportion of patients achieved clinical improvement and improvement in rectal bleeding in the balsalazide group vs. the placebo group (55 vs. 40%, P=0.02). The most common adverse events reported were worsening of UC and headache; both were reported more often in the placebo group.\n Balsalazide disodium 1.1 g tablets administered as 3.3 g twice daily are effective, well tolerated and significantly better than placebo for improving signs and symptoms of mild-to-moderately-active UC. This new formulation with a reduced pill and dosing burden offers the potential to improve convenience and compliance in patients with active UC.", "The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX) has been proposed as a novel approach for the treatment of ulcerative colitis (UC).\n To assess the efficacy and the tolerability of 8 weeks' oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates.\n This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS).\n A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005).\n CB-01-05 MMX was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates.", "To study the different therapy for different types of ulcerative colitis (UC) in China.\n Among 102 UC patients, 42 chronic relapse type UC patients were randomly divided into olsalazine sodium treatment group (n=21) and SASP group (n=21). Clinical effects and safety were observed in the 2 groups. Forty-two first episode type UC patients were randomly divided into Heartleaf houttuynia herb treatment group (n=21) and SASP group (n=21). Clinical effects were observed in the 2 groups while ultrastructure of colonic mucosa, ICAM-1 and the pressure of distant colon were studied in Heartleaf houttuynia herb group. Eighteen patients (8 males, 10 females) with refractory UC and unresponsive to high-dose prednisolone and sulfasalazine therapy more than one month were treated with Kangshuanling (7200 U/d). Prednisolone was gradually stopped and sulfasalazine was maintained. Stool frequency, rectal bleeding, colonoscopy, general well-being, histology were observed and CD62p, CD63, CD54, Pgp-170 (flow cytometry), TXA2 (RIA), blood platelet aggregation rate and thrombosis length in vitro were assessed.\n In the 42 chronic relapse type UC patients, the overall clinical effects of olsalazine sodium group (complete remission in 16, improvement in 4, inefficiency in 1) were better than those of SASP group (complete remission in 10, improvement in 4, inefficiency in 7, P<0.05). Symptomatic remission of olsalazine sodium group (complete remission in 15, partial remission in 5, inefficiency in 1) was better than that of SASP group (complete remission in 10, partial remission in 5, inefficiency in 6, P<0.05). The colonoscopic remission of olsalazine sodium group(complete remission in 11, partial remission in 9, inefficiency in 1) was better than that of SASP group (complete remission in 7, partial remission in 8, inefficiency in 6, P<0.05). The histologic remission of olsalazine sodium group (complete remission in 13, partial remission in 7, inefficiency in in 1) was better than that of SASP group (complete remission in 6, partial remission in 10, inefficiency in 5, P<0.05). The side effects of gastrointestinal tract in olsalazine sodium group were less than those of SASP group except for frequency of watery diarrhea. No other side effects were observed in olsalazine sodium group while ALT increase, WBC decrease and skin eruption were observed in SASP group. Two patients relapsed in olsalazine sodium group while 8 cases relapsed in SASP group during the flow-up period (from six months to one year). In the 42 first episode type UC patients, the clinical effect of Heartleaf houttuynia herb group (complete remission in 20, 95.2%; improvement in 1, 4.8%) was better than that of SASP group (complete remission in 15, 72.4%, improvement in 5, 23.8%; inefficiency in 1, 3.8%, P<0.01). The time of stool frequency recovering to normal (5.6+/-3.3 d), and blood stool disappearance (6.7+/-3.8 d) and abdominal pain disappearance (6.1+/-3.5 d) in Heartleaf houttuynia herb group was all shorter than that in SASP group (9.5+/-4.9 d, 11.7+/-6.1 d, 10.6+/-5.3 d, P<0.01). Heartleaf houttuynia herb could inhibit the epithelial cell apoptosis of colonic mucous membrane and the expression of ICAM-1 (45.8+/-5.7% vs 30.7+/-4.1%, P<0.05). Compared with normal persons, the mean promotive speed of contraction wave stepped up (4.6+/-1.6 cm/min vs 3.2+/-1.8 cm/min, P<0.05) and the mean amplitude of the wave decreased (14.2+/-9.3 kPa vs 18.4+/-8.0 kPa, P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, these 2 indexes improved significantly (17.3+/-8.3 kPa, 3.7+/-1.7 cm/min, P<0.05). In normal persons, the postprandial pressure of sigmoid (2.9 +/-0.9 kPa) was higher than that of descending colon (2.0+/-0.7 kPa) and splenic flexure (1.7+/-0.6 kPa), while the colonic pressure (1.5+/-0.5 kPa, 1.4+/-0.6 kPa, 1.3+/-0.6 kPa) decreased significantly (P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold of distant colon (67.3+/-18.9 mL) in active UC patients decreased significantly compared with that of normal persons (216.2+/-40.8 mL, P<0.05) and recovered to normal after treatment with Heartleaf houttuynia herb(187.4+/-27.2 mL, P<0.05). In the 18 refractory UC patients with platelet activation, after more than 4 wk of combined Kangshuanling and sulfasalazine therapy, 16 patients achieved clinical remission, with a highly significant statistical difference (P<0.01) between pre-and post-treatment mean scores for all disease parameters: stool frequency (8.2/d vs 1.6/d), rectal bleeding (score 2.7 vs 0.3), colonoscopy (score 2.6 vs 1.1), histology (score 12.0 vs 5.0), general well being (score 4.0 vs 0.6) and CD62p (8.0+/-3.1% vs 4.1+/-1.8%), CD63 (6.3+/-2.1% vs 3.2+/-1.6%), TXA2 (548+/-85 ng/L vs 390+/-67 ng/L), platelet aggregation rate (43.2+/-10.7% vs 34.8+/-8.1%), thrombosis length in vitro (2.3+/-0.6 cm vs 1.8+/-0.3 cm), CD54 in blood (26.9+/-6.9% vs 14.4+/-5.1%), CD54 in tissues (51.1+/-6.2% vs 23.1+/-4.1%), Pgp-170 in blood (18.9+/-3.9% vs 10.4+/-2.7%), Pgp-170 in tissues (16.5+/-3.2% vs 10.2+/-2.3%, P<0.01 or 0.05).\n Based on the characteristics of UC cases in China, different therapy should be given to different types of UC with expected satisfactory results.", "It is not clear what induction dose of mesalamine is optimal for treating patients with mildly and moderately active ulcerative colitis (UC). This study was conducted to determine the efficacy and safety of mesalamine 4.8 g/day compared with 2.4 g/day for the treatment of moderately active UC.\n A multicenter, randomized, double-blind, 6-week, active-control study (ASCEND III) was conducted to assess the noninferiority of delayed-release mesalamine 4.8 g/day (Asacol HD, 800-mg tablet; Procter & Gamble, Pharmaceuticals, Inc, Mason, Ohio) with 2.4 g/day (Asacol, 400-mg tablet; Procter & Gamble Pharmaceuticals, Inc) in 772 patients with moderately active UC. The primary endpoint was treatment success (overall improvement) at week 6, defined as improvement in the Physician's Global Assessment (based on clinical assessments of rectal bleeding, stool frequency, and sigmoidoscopy), with no worsening in any individual clinical assessment.\n The primary objective of noninferiority was met. Seventy percent (273 of 389) of patients who received 4.8 g/day of mesalamine achieved treatment success at week 6, compared with 66% (251 of 383) of patients receiving 2.4 g/day (95% confidence interval for 2.4 g/day minus 4.8 g/day, -11.2 to 1.9). In addition, 43% of patients who received 4.8 g/day mesalamine achieved clinical remission at week 6 compared with 35% of patients who received 2.4 g/day (P = .04). A therapeutic advantage for the 4.8 g/day dose was observed among patients previously treated with corticosteroids, oral mesalamines, rectal therapies, or multiple UC medications. Both regimens were well-tolerated with similar adverse events.\n Delayed-release mesalamine 4.8 g/day (800-mg tablet) is efficacious and well-tolerated in patients with moderately active UC.", "Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder.\n To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC.\n Randomized, double-blind, placebo-controlled trial of patients (n=209 MG, n=96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding=0, mucosal appearance <2] who took MG 1.5 g or placebo once-daily for up to 6 months. Primary efficacy endpoint: the percentage of patients who remained relapse-free at month 6/end of treatment. Relapse was defined as SDAI rectal bleeding score ≥1 and a mucosal appearance score ≥2, a UC flare, or initiation of medication to treat a UC flare.\n The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo (78.9% vs. 58.3%, P < 0.001) in the intent-to-treat analysis. Significant differences (P ≤ 0.025) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding, physician's disease activity rating, stool frequency, the SDAI at month 6/end of treatment, patients classified as a treatment success and relapse-free duration. The incidence of adverse events was similar between groups.\n Once-daily mesalamine (mesalazine) was effective in maintaining remission of UC for 6 months.\n © 2010 Salix Pharmaceuticals.", "Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment of patients with proximal lower limb DVT.\n 201 patients with proximal lower limb DVT from 13 centers in Brazil were randomized in an open manner to receive either enoxaparin [1.5 mg/kg subcutaneous (s.c.) OD] or intravenous (i.v.) UFH (adjusted to aPTT 1.5-2.5 times control) for 5-10 days. All patients also received warfarin (INR 2-3) for at least 3 months. The primary efficacy endpoint was recurrent DVT (confirmed by venography or ultrasonography), and safety endpoints included bleeding and serious adverse events. The rate of pulmonary embolism (PE) was also collected. Hospitalization was at the physician's discretion.\n Baseline patient characteristics were comparable between groups. The duration of hospital stay was significantly shorter with enoxaparin than with UFH (3 versus 7 days). In addition, 36% of patients receiving enoxaparin did not need to be hospitalized, whereas all of the patients receiving UFH were hospitalized. The treatment duration was slightly longer with enoxaparin (8 versus 7 days). There was a nonsignificant trend toward a reduction in the rate of recurrent DVT with enoxaparin versus UFH, and similar safety.\n A once-daily regimen of enoxaparin 1.5 mg/kg subcutaneous is at least as effective and safe as conventional treatment with a continuous intravenous infusion of UFH. However, the once daily enoxaparin regimen is easier to administer (subcutaneous versus intravenous), does not require aPTT monitoring, and leads to both a reduced number of hospital admissions and an average 4-day-shorter hospital stay.", "Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects.\n To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC.\n Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters.\n A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P < 0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group.\n BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis." ]

[ "8473466", "9853762", "8203435", "7672654", "8018618", "15656211", "16253978", "11679528", "2115379" ]

[ "Pre-operative gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata.", "Treatment with a gonadotrophin releasing hormone agonist before hysterectomy for leiomyomas: results of a multicentre, randomised controlled trial.", "Gonadotropin-releasing hormone agonist use before hysterectomy.", "[Preoperative management of uterine leiomyomatosis using pituitary gonadotropin-releasing hormone analogues].", "Treatment with the gonadotrophin releasing hormone-agonist goserelin before hysterectomy for uterine fibroids.", "Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study.", "A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients.", "Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III-IV: a randomized controlled trial.", "Treatment with GnRH agonists before myomectomy and the risk of short-term myoma recurrence." ]

[ "To determine whether pre-operative treatment with gonadotrophin-releasing hormone (GnRH) analogue may have a beneficial effect on surgery outcome, 53 patients with symptomatic fibroid uteri awaiting myomectomy or transabdominal hysterectomy (TAH), were randomly divided into a study group (n = 29) and a control group (n = 24). The study group of patients were treated by an i.m. injection of D-Trp6 LHRH microcapsules at 2 months and 1 month prior to surgery. The control group had no pre-operative treatment. Haemoglobin concentration and oestradiol, follicle-stimulating hormone and luteinizing hormone concentrations were measured at 2 months and 1 month prior to surgery, and at surgery. The duration of surgery was shorter in the study group (49 versus 70 min in the hysterectomy group) and intra-operative blood loss was less (208 versus 309 ml in the hysterectomies and 320 versus 476 ml in the myomectomies). Pre-operative treatment with GnRH-agonists which induces shrinkage of the uterus and fibroids is therefore efficient in shortening the duration of surgery, and diminishing the intra-operative blood loss in surgery for fibroid uteri. Such pre-operative treatment is therefore a useful addition to surgery in cases with symptomatic fibroid uteri.", "To ascertain whether uterine shrinkage induced by a gonadotrophin releasing hormone agonist before hysterectomy for fibroids increases the possibility of a vaginal procedure.\n A multicentre, prospective, randomised, controlled study.\n One hundred and twenty-seven premenopausal women with a uterine volume of 12 to 16 gestational weeks.\n Twelve weeks of triptorelin depot treatment before hysterectomy or immediate surgery.\n Number of vaginal and abdominal hysterectomies, operating time, blood loss, degree of difficulty of the procedure, perioperative serum haemoglobin and haematocrit levels, hospital stay, and patients' overall satisfaction with treatment.\n After randomisation, four women withdrew from the study, leaving 60 women in the triptorelin arm and 63 in the immediate surgery arm. At baseline evaluation a vaginal hysterectomy was indicated in seven women allocated to pre-operative medical therapy (12%), and in 10 of those allocated to immediate surgery (16%). Clinical assessment after the 12-week GnRH agonist course showed that abdominal hysterectomy was no longer indicated in 25/53 women (47%) as a vaginal procedure appeared appropriate. Thus the overall rate of indication for a vaginal procedure in the pre-operative medical treatment arm was 32/60 cases (53%), with a between-group difference of 37% (95% CI, 26% to 51%; chi2(1) = 19.18, P < 0.0001; OR 6.06; 95% CI, 2.60 to 14.10). Pre- and post-operative serum haemoglobin and haematocrit levels were significantly higher in the GnRH agonist than in the immediate surgery arm. No appreciable difference was observed between the groups in the other intra- and post-operative variables, including patients' satisfaction.\n Pre-operative GnRH agonist therapy increased the rate of vaginal hysterectomy in selected women with fibroids and uterine volume of 12 to 16 gestational weeks.", "Our purpose was to compare the effects of leuprolide acetate in patients with symptomatic uterine leiomyoma before hysterectomy.\n Group I (n = 90) included patients with a pretreatment uterine size of 14 to 18 gestational weeks and group II (n = 60) included patients with uteri > 18 weeks' gestational size. Patients in both groups were randomized to either immediate hysterectomy or 2 months of preoperative gonadotropin-releasing hormone agonist.\n All patients in the two groups with a pretreatment hemoglobin < 11.0 gm/dl randomized to agonist had a significant (p < 0.05) increase (> or = 1.5 gm/dl) in hemoglobin level. Patients in group I who received preoperative agonist were more likely to undergo vaginal hysterectomy (80% vs 13%, p < 0.05) than were patients who did not receive preoperative agonist. Patients undergoing vaginal hysterectomy had a shorter hospital stay, decreased operative blood loss, and a shorter convalescence period than did those undergoing abdominal hysterectomy. In group II, in spite of a mean uterine volume reduction of 51.3%, intraoperative morbidity, operative blood loss, hospital stay, and postoperative convalescence period did not differ between treatment arms.\n The preoperative administration of gonadotropin-releasing hormone agonist in patients with a uterus of 14 to 18 weeks' size increases the use of vaginal hysterectomy, decreases intraoperative blood loss, and shortens hospital stay and convalescence. Preoperative gonadotropin-releasing hormone agonist for patients with a preoperative hemoglobin < 11.0 gm/dl reduces the risk of preoperative transfusion. Preoperative gonadotropin-releasing hormone use in the nonanemic patient with a uterine size > or = 18 weeks' gestational size doses not appear to lower operative morbidity.", "Uterine leiomyomatosis shows a frequency from 25 to 30% in reproductive age women. Traditional treatment is hysterectomy or myomectomy independently from fertility wishes of the woman. Its growth has been associated to estrogenic activity. Because of this, several substances have been used to diminish tumour size, pre-operatively. The use of analogues of liberating hormone of hypophysiary gonadotropins (GnRH), given to favor surgical technique, to diminish trans-operative bleeding and to avoid blood transfusions. Clinical efficiency of the use of nafarelin acetate in women with uterine leyomiomatosis, pre-operatively during three months, was studied in this paper. The study was prospective, comparative, blind and with longitudinal measurements. Twenty eight women were included. Group I (n = 13) and Group II (n = 15) control without treatment. Observation units included FSH, LH, E2, BHC, HCT, USG basal, 30, 60, 90 days. Results showed a diminution of more than 80% of the initial uterine volume, and of 30% of the myomas independently measured. Side effects, tolerance and efficacy of the used compound, are mentioned.", "To investigate the effect of the gonadotrophin releasing hormone (GnRH)-agonist goserelin, given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata, on the pre-operative symptoms, difficulty of operation and operative blood loss.\n Randomised placebo-controlled study.\n Patients were recruited from the gynaecological outpatient departments from hospitals in Edinburgh, Glasgow and Newcastle.\n Seventy-one premenopausal women with uterine leiomyomata who were on the waiting list for hysterectomy.\n After the presence of leiomyomata was confirmed using ultrasonography, the women were randomised to receive either the GnRH-agonist goserelin by monthly subcutaneous injection or a sham injection for three months prior to operation. At the monthly visits, patients were asked about treatment related symptoms, fibroid related symptoms, and their bleeding patterns. Blood was taken for haematological assessment.\n Haemoglobin concentrations at recruitment, at operation and post-operatively, pre-operative symptoms, operative difficulty and blood loss and post-operative complications.\n Treatment with goserelin induced amenorrhoea in over 80% of the women, and this was associated with a significant rise in haemoglobin level. At the time of operation, fibroid related symptoms were less in the goserelin group than in the placebo group. The hysterectomy was technically easier and the median (range) operative blood loss was significantly lower in the goserelin group compared with the placebo group (187 (60-600) ml vs 308 (118-1000) ml respectively; P < 0.05, Wilcoxon signed rank test). There was no difference between the two groups in the duration of hospital stay or the frequency of post-operative complications. The fibroids were smaller at the time of operation in the goserelin group, and more women treated with goserelin were able to have their operations through a transverse incision.\n This study demonstrates the benefits of goserelin in women having total abdominal hysterectomy for uterine leiomyomata.", "To assess the effect of short-term use of a gonadotropin releasing hormone (GnRH) analogue for 3 months before ovarian stimulation in patients with stage III and IV endometriosis after conservative surgery.\n Eleven patients were randomly selected to receive intramuscular injections of GnRH analogue, leuprolide acetate (3.75 mg), every 28 days, or 400 mg danazol orally 2 times per day for 3 months before ovarian stimulation after conservative laparoscopic or laparotomy surgeryfor stage III and IV symptomatic endometriosis (group 1), as compared with 30 patients who had received no postoperative treatment with GnRH analogue or danazol but underwent ovarian stimulation immediately after thefirst menses within 3 months postoperatively (group 2).\n Although the number of oocytes retrieved and number of embryos per cycle were significantly higher in group 1, the pregnancy rate per cycle in group 1 was not significantly different from that in group 2 (18% vs. 20%). The cumulative pregnancy rate at 12 months was 54.5% and 56.7% in group 1 and group 2, respectively. With regard to recurrence of disease after 24 months of follow-up, group 2 had a statistically significantly higher recurrence rate (13.3%) than did group 1 (0%).\n Short-term use of GnRH analogue before ovarian stimulation in women with stage III or IV endometriosis confers no definite benefits on pregnancy rates per cycle when compared with patients who received ovarian stimulation within 3 months after conservative surgery.", "This randomized controlled trial was designed to assess the impact of oral contraceptive (OC) scheduling with a GnRH antagonist (ganirelix) regimen on the ovarian response of women undergoing recombinant FSH (rFSH) stimulation for IVF, compared with a non-scheduled ganirelix regimen and a long GnRH agonist (nafarelin) protocol.\n A total of 110 women was treated with an OC and ganirelix, 111 with ganirelix alone and 111 with nafarelin. The OC (containing 30 microg ethinylestradiol/150 microg desogestrel) was taken for 14-28 days and stopped 2 days prior to the start of rFSH treatment. Primary efficiency parameters were the number of cumulus-oocyte complexes (per attempt) and the number of grade 1 or 2 embryos (per attempt).\n In terms of follicular growth and hormone profiles, the OC-scheduled antagonist regimen mimicked the agonist regimen rather than the (non-scheduled) GnRH antagonist regimen. In the OC-scheduled GnRH antagonist group and the nafarelin group (versus the non-scheduled antagonist group), pituitary suppression was more profound at the start of stimulation (P < or = 0.001), there was a slower start of follicular growth (P < or = 0.001), longer stimulation was required (11.7 and 10.3 days respectively versus 9.4; P < or = 0.001), and more rFSH was used (2667 and 2222 IU versus 1966 IU; P < or = 0.001). In the three groups, the number of oocytes was similar (13.1, 12.9 and 11.5 respectively; not significant) as well as the number of good quality embryos (5.1, 5.7 and 5.0 respectively; not significant).\n OC treatment prior to the rFSH/ganirelix regimen can be successfully applied to schedule patients, although more days of stimulation and more rFSH are required than with a non-scheduled GnRH antagonist regimen.", "In order to decrease endometriosis recurrence after surgical therapy, it has been proposed to use a post-surgical oestrogen-lowering medical treatment. Results from previous trials on this topic are contradictory.\n A total of 89 women were randomized, by computer-generated list, after laparoscopic conservative surgery for symptomatic endometriosis stage III-IV to receive monthly i.m. injections of gonadotrophin-releasing hormone (GnRH) analogue, leuprolide acetate depot (3.75 mg) for 3 months (n = 44) or to an expectant management (n = 45). All patients were followed up every 6 months for evaluation of pain symptoms, fertility and objective disease recurrence.\n During the follow-up, which ranged from 6-36 months, five (33%) of the 15 women who wanted children and who were allocated the GnRH analogue and six (40%) of the 15 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during the follow-up in 10 (23%) of the women allocated the GnRH analogue and 11 (24%) of those allocated no treatment; the cumulative pain recurrence rates at 18 months were 23 and 29% respectively (not significant). Four women (9%) treated with GnRH analogue and four women (9%) who received no treatment had objective disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography.\n This study does not support the routine post-operative use of a 3 month course of GnRH analogue in women with symptomatic endometriosis stage III-IV.", "Twenty-four women with symptomatic multiple uterine myomas were allocated randomly to treatment with buserelin, 1200 micrograms/day intranasally, for 3 months followed by myomectomy (n = 8) or to immediate myomectomy (n = 16). Pre-operative treatment with buserelin reduced the mean uterine volume from 432 (SD 165) to 242 (SD 82) ml (P less than 0.01) but intra-operative blood loss and postoperative morbidity were not significantly less in this group. Six months after operation, pelvic examination was normal in all the patients. However, ultrasonography with transvaginal probe demonstrated the presence of myomas of less than 1.5 cm in five women (63%) treated pre-operatively with the analogue and in two women (13%) who underwent immediate surgery (P less than 0.05). Induction of a period of hypo-oestrogenism before myomectomy seems to favour short-term recurrence of uterine myomas, limiting the efficacy of surgery." ]

[ "8455969", "19853518", "2140432", "15082950", "9252001", "15109505", "2363027", "6601789", "19920718" ]

[ "TENS for children's procedural pain.", "Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain.", "A controlled trial of transcutaneous electrical nerve stimulation (TENS) and exercise for chronic low back pain.", "Evaluation of TENS during screening flexible sigmoidoscopy.", "Transcutaneous nerve stimulation (TENS) during the first stage of labour: a randomized clinical trial.", "Pain reducing effect of three types of transcutaneous electrical nerve stimulation in patients with chronic pain: a randomized crossover trial.", "Comparison of TENS treatments in hemiplegic shoulder pain.", "Transcutaneous electrical nerve stimulation (TENS) as compared to placebo TENS for the relief of acute oro-facial pain.", "Transcranial DC stimulation coupled with TENS for the treatment of chronic pain: a preliminary study." ]

[ "A 3 x 6 factorial design with a double blind and placebo control was employed to investigate the effect of TENS treatment on pain produced by venipuncture. The three treatment groups consisted of TENS, placebo-TENS and control. Subjects were blocked into six 2-year age groups (ages: 5-17 years). During the period of the study, 896 children attending the outpatient laboratory of a general hospital were screened and 514 children completed the study. The data which were collected before venipuncture included expected pain and state anxiety. Following venipuncture, pain intensity was measured with a vertical visual analogue scale (VAS) and pain affect was assessed with McGrath's faces scale. Significant main effects for treatment and age groups were obtained. Pain intensity and affect were lowest for the TENS group and highest for the control group. The pain scores were greatest for lower age groups and lowest for higher age groups. The results of this study support the use of TENS for children's pain and the need for interventions for children's procedural pain.", "This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain.\n Cancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial.\n Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.", "A number of treatments are widely prescribed for chronic back pain, but few have been rigorously evaluated. We examined the effectiveness of transcutaneous electrical nerve stimulation (TENS), a program of stretching exercises, or a combination of both for low back pain. Patients with chronic low back pain (median duration, 4.1 years) were randomly assigned to receive daily treatment with TENS (n = 36), sham TENS (n = 36), TENS plus a program of exercises (n = 37), or sham TENS plus exercises (n = 36). After one month no clinically or statistically significant treatment effect of TENS was found on any of 11 indicators of outcome measuring pain, function, and back flexion; there was no interactive effect of TENS with exercise. Overall improvement in pain indicators was 47 percent with TENS and 42 percent with sham TENS (P not significant). The 95 percent confidence intervals for group differences excluded a major clinical benefit of TENS for most outcomes. By contrast, after one month patients in the exercise groups had significant improvement in self-rated pain scores, reduction in the frequency of pain, and greater levels of activity as compared with patients in the groups that did not exercise. The mean reported improvement in pain scores was 52 percent in the exercise groups and 37 percent in the nonexercise groups (P = 0.02). Two months after the active intervention, however, most patients had discontinued the exercises, and the initial improvements were gone. We conclude that for patients with chronic low back pain, treatment with TENS is no more effective than treatment with a placebo, and TENS adds no apparent benefit to that of exercise alone.", "The expectation of pain is a statistically significant factor negatively affecting patient compliance with current screening flexible sigmoidoscopy recommendations. Numerous pain reduction modalities have been studied with limited success. Transcutaneous electrical nerve stimulation (TENS) has been used to treat pain of various origins. The purpose of this pilot study was to determine the efficacy of TENS in reducing discomfort experienced during screening flexible sigmoidoscopy.A double-blind study was conducted in which 90 subjects were randomized to receive TENS, sham TENS, or control (standard care). The same pulse frequency and intensity were used for all subjects in the TENS group. Subjects completed preprocedural and postprocedural questionnaires, and the endoscopist completed a postprocedural questionnaire. A slight, but statistically insignificant (p =.526) reduction in the mean pain score reported by the TENS group was noted when compared with the sham TENS and control groups (2.00, 2.27, and 2.23 respectively). In light of the fact that only one pulse frequency and intensity of the TENS intervention were used in this study, further study with this safe and cost-effective modality is warranted.", "Our objective was to study the efficacy of transcutaneous electrical nerve stimulation (TENS) in reducing pain during the first stage of labour. Using a prospective randomized placebo-controlled, double blind clinical trial, a patient-controlled analgesia system was used to measure differences in outcome. Trials took place in a labour unit at the St. Antonius Hospital, Nieuwegein, The Netherlands, during a period of 18 months. Forty-six patients, during the first stage of labour, were treated with TENS, and 48 with a placebo apparatus. Main outcome measures were pain relief, amount of administered analgesics, obstetrical and neonatal outcome, and side effects. No significant differences occurred between groups in the number of requests for pethidine/promethazine. The foetal outcome in both groups was the same. TENS and placebo were considered equally effective by both patients and staff. In conclusion, TENS was not more effective than a placebo apparatus in relieving pain during the first stage of labour. No adverse side-effects occurred.", "Transcutaneous electrical nerve stimulation (TENS) is a frequently applied therapy in chronic pain although evidence for effectiveness is inconclusive. Several types of TENS, based on different combinations of frequency, pulse duration and intensity, exist. The precise mechanism of action and the relevance of combinations of stimulus parameters are still unclear. To compare the effectiveness of three types of TENS we conducted a randomized, single blinded crossover trial. Patients received two times a 2-week period of daily TENS treatment, separated by a washout period of 2 weeks. In total, 180 chronic pain patients were randomized into three groups. In group 1, high frequency, low intensity TENS (HFT) was compared with high frequency, high intensity TENS (HIT). In groups 2 and 3, HFT and HIT were compared with a control TENS (COT). The order of applying the different modalities of TENS in each group was also randomized. Primary outcome was the patient's overall assessment of effectiveness and pain reduction (VAS). No differences were found in patient's assessment or pain reducing effect between the three groups, indicating no superiority of one type of TENS. In total, 56% continued TENS after the 2-week treatment period. At 6 months, 42% of all patients still used TENS. We concluded that there were no differences in effectiveness for the three types of TENS used in this study. Because no placebo group was included, no definite conclusions on effectiveness of TENS in general in the treatment of chronic pain could be made.", "The aim of this paper is to evaluate the effectiveness of high-intensity versus low-intensity transcutaneous electrical nerve stimulation (TENS) and versus placebo for treatment of hemiplegic shoulder pain. Three groups of 20 patients each (A, B, C) were studied. In group A high-intensity TENS was delivered at 3 times the sensory threshold with frequency of 100 Hz; in group B low-intensity TENS was delivered at the sensory threshold with frequency of 100 Hz. Group C received placebo stimulation. The treatment protocol consisted of 12 sessions (4 weeks). Before treatment, at the end of it and one month after, passive range of motion (PROM) for flexion, extension, abduction and external rotation were evaluated. Statistically significant improvements of PROMs were recorded for group A, but not for groups B or C.", "The present paper describes the effect of high frequency, low frequency and placebo TENS on acute oro-facial pain in 62 patients, attending to an emergency clinic for dental surgery; they had all suffered pain for 1-4 days. The patients were randomly assigned to one of three groups receiving either high frequency (100 Hz), low frequency (2 Hz) or placebo TENS. In the two groups receiving TENS (42 patients) 16 patients reported a reduction in pain intensity exceeding 50%; out of these 16 patients, 4 patients reported complete relief of pain. In the placebo group (20 patients) 2 patients reported a pain reduction of more than 50%; out of these 2 patients, none reported a complete pain relief. Mechanical vibratory stimulation augmented the pain reduction obtained by TENS in 5 out of 10 patients.", "Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation [transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation.\n We performed a preliminary, randomized, sham-controlled, crossover, clinical study in which 8 patients were randomized to receive active tDCS/active TENS (\"tDCS/TENS\" group), active tDCS/sham TENS (\"tDCS\" group), and sham tDCS/sham TENS (\"sham\" group) stimulation. Assessments were performed immediately before and after each condition by a blinded rater.\n The results showed that there was a significant difference in pain reduction across the conditions of stimulation (P=0.006). Post hoc tests showed significant pain reduction as compared with baseline after the tDCS/TENS condition [reduction by 36.5% (+/-10.7), P=0.004] and the tDCS condition [reduction by 15.5% (+/-4.9), P=0.014], but not after sham stimulation (P=0.35). In addition, tDCS/TENS induced greater pain reduction than tDCS (P=0.02).\n The results of this pilot study suggest that the combination of TENS with tDCS has a superior effect compared with tDCS alone." ]

[ "20833738", "20169461", "20605876", "12209517", "19369404", "16221103", "16820790", "12840090", "15082482" ]

[ "Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial.", "Is mycophenolate mofetil superior to pulse intravenous cyclophosphamide for induction therapy of proliferative lupus nephritis in Egyptian patients?", "Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.", "Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.", "Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.", "Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis.", "Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial.", "A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies.", "EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis." ]

[ "Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment.\n A total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months.\n The baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out.\n Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.", "Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis. The aim of this study was to evaluate the efficacy of MMF compared with IVC in the induction therapy of proliferative lupus nephritis.\n We randomly assigned 47 patients with newly diagnosed active proliferative lupus nephritis class III or IV to open-label oral MMF 2 g/day for 6 months or intravenous cyclophosphamide 0.5-1 g/m(2) monthly for 6 months in addition to corticosteroids.\n In the intention-to-treat analysis, 14 of the 24 patients (58.33%) receiving MMF and 12 of the 23 patients receiving cyclophosphamide (52.17%) had remission (P = 0.48); complete remission occurred in 6 of the 24 patients (25%) and 5 of the 23 patients (21.74%), respectively (P = 0.53). Improvements in packed cell volume, the erythrocyte sedimentation rate, anti-double-stranded DNA antibodies titer (anti-dsDNA), serum complement, proteinuria, urinary activity, renal function, serum soluble interleukin-2 receptor alpha concentration and the systemic lupus activity measure score were similar in both groups. Two patients assigned to MMF and another patient assigned to IVC developed end-stage renal failure with commencement of dialysis. Adverse events were similar. Major infections occurred in two patients in each group. There was no difference in gastrointestinal side effects, but more diarrhea occurred in those receiving MMF.\n In this 24-week trial, MMF or IVC combined with corticosteroids demonstrated equal efficacy in inducing remission of proliferative lupus nephritis.", "Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)", "Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment.\n In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed.\n Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant.\n The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.", "Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.", "The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis.\n Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were randomly assigned to either mycophenolate mofetil (MMF) 2 g/day for 6 months or intravenous cyclophosphamide (IVC) 0.75-1 g/m(2) monthly for 6 months in addition to corticosteroids.\n Remission occurred in 13 out of 25 patients (52%) in the IVC group and 11 out of 19 patients (58%) in the MMF group (P = 0.70). There were 12% in the IVC group and 26% in the MMF group that achieved complete remission (P = 0.22). Improvements in haemoglobin, the erythrocyte sedimentation rate, serum albumin, serum complement, proteinuria, urinary activity, renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups. Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups. The chronicity index increased in both groups but was only significant in the IVC group. Adverse events were similar. Major infections occurred in three patients in each group. There was no difference in gastrointestinal side-effects.\n MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis.", "Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), we randomized 87 proliferative LN patients to either cyclophosphamide pulses (750 mg/m(2), 13 pulses in 2 years) combined with oral prednisone (CY) or to azathioprine (2 mg/kg/day in 2 years) combined with intravenous pulses of methylprednisolone (3 x 3 pulses of 1000 mg) and oral prednisone (AZA). After a median follow-up of 5.7 years (interquartile range 4.1-7.2 years), doubling of serum creatinine was more frequent in the AZA group, although not statistically significant (relative risk (RR): 4.1, with 95% confidence interval (95% CI): 0.8-20.4). Relapses occurred more often in the AZA group (RR: 8.8, 95% CI: 1.5-31.8). Creatinine and proteinuria at last visit did not differ between the two treatment arms. Moreover, 88.4% of the patients in the AZA arm were still free of cyclophosphamide treatment. During the first 2 years, the frequency of remission was not different, but infections, especially herpes zoster virus infections (HZV) were more frequent in the AZA group. Parameters for ovarian function did not differ between the two groups. In conclusion, in this open-label randomized controlled trial, cyclophosphamide was superior to azathioprine with regard to renal relapses and HZV. At last follow-up, there were no differences in serum creatinine or proteinuria between the two groups. However, since our study lacked sufficient power, longer follow-up is needed to reveal putative differences.", "The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission.\n We studied patients with a new diagnosis of generalized vasculitis and a serum creatinine concentration of 5.7 mg per deciliter (500 micromol per liter) or less. All patients received at least three months of therapy with oral cyclophosphamide and prednisolone. After remission, patients were randomly assigned to continued cyclophosphamide therapy (1.5 mg per kilogram of body weight per day) or a substitute regimen of azathioprine (2 mg per kilogram per day). Both groups continued to receive prednisolone and were followed for 18 months from study entry. Relapse was the primary end point.\n Of 155 patients studied, 144 (93 percent) entered remission and were randomly assigned to azathioprine (71 patients) or continued cyclophosphamide (73 patients). There were eight deaths (5 percent), seven of them during the first three months. Eleven relapses occurred in the azathioprine group (15.5 percent), and 10 occurred in the cyclophosphamide group (13.7 percent, P=0.65). Severe adverse events occurred in 15 patients during the induction phase (10 percent), in 8 patients in the azathioprine group during the remission phase (11 percent), and in 7 patients in the cyclophosphamide group during the remission phase (10 percent, P=0.94 for the comparison between groups during the remission phase). The relapse rate was lower among the patients with microscopic polyangiitis than among those with Wegener's granulomatosis (P=0.03).\n In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse. Thus, the duration of exposure to cyclophosphamide may be safely reduced.\n Copyright 2003 Massachusetts Medical Society", "To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE).\n A multicentre randomised controlled trial was conducted between June 1992 and May 1996 involving eight European centres. All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis. All received corticosteroids in addition to cytotoxic drugs, as defined in the protocol, for two years. The trial was terminated after four years as recruitment was disappointing.\n 32 SLE patients with lupus nephritis were recruited: 16 were randomised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine. Mean duration of follow up was 3.7 years in the continuous group (range 0 to 5.6) and 3.3 years in the pulse group (range 0.25 to 6). Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis. Two patients in the continuous therapy group developed end stage renal failure requiring dialysis, but none in the intermittent pulse therapy (p = 0.488; NS). There were similar numbers of side effects and withdrawals from treatment in both groups. There were three deaths: two in the intermittent pulse therapy group and one in the continuous therapy group.\n There was no statistically significant difference in efficacy and side effects between the two regimens. Infectious complications occurred commonly, so careful monitoring is required during treatment." ]

[ "16243954", "12755982", "8737434", "16737346", "15066200", "12356708", "15659884", "12817353", "15188323" ]

[ "A multifaceted intervention according to the Audit Project Odense method improved secondary prevention of ischemic heart disease: a randomised controlled trial.", "Recurrent aphthous stomatitis unresponsive to topical corticosteroids: a study of the comparative therapeutic effects of systemic prednisone and systemic sulodexide.", "Small group intervention vs formal seminar for improving appropriate drug use.", "Rational prescribing in primary care (RaPP): a cluster randomized trial of a tailored intervention.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].", "Educational strategies to promote evidence-based community pharmacy practice: a cluster randomized controlled trial (RCT).", "Multidisciplinary HIV adherence intervention: a randomized study.", "Modifying dyspepsia management in primary care: a cluster randomised controlled trial of educational outreach compared with passive guideline dissemination.", "Multifaceted intervention to improve rheumatologists' management of glucocorticoid-induced osteoporosis: a randomized controlled trial." ]

[ "No single quality improvement instrument has proved consistently effective, but multifaceted interventions are believed to have the greatest impact. However, only little is known regarding what combinations are likely to be successful.\n To evaluate the impact of a multifaceted intervention strategy combining GP registrations, outreach visits and feedback, targeting secondary prevention of ischemic heart disease in general practice.\n A randomised controlled trial including 28 GPs in Ringkjøbing County, Denmark. Half of the GPs received outreach visits and feedback on their prescribing of heart disease drugs. Evaluation was based on registration of consultations with patients suffering from ischemic heart disease.\n The intervention had a statistically significant impact on prescribing of lipid lowering drugs [odds ratio 1.59; 95% confidence interval (CI) 1.00 to 2.53] and acetylsalicylic acid (odds ratio 2.54; 95% CI 1.21 to 5.31).\n An intervention strategy combining outreach visits, feedback and GP registrations is a promising way of improving the quality of preventive treatment in general practice.", "Recurrent aphthous stomatitis (RAS) is a common oral condition, the etiology of which remains largely unclear. Numerous therapeutic protocols have been tried. Apart from immunomodulators, no therapy is unequivocally effective, and many systemic therapies have potential adverse effects.\n To compare, in patients with frequent RAS unresponsive to conventional therapies, the therapeutic effectiveness of systemic prednisone with that of systemic sulodexide, a low-molecular-weight heparin with immunosuppressive activity but few adverse effects.\n The study involved a group of 30 patients suffering from frequent minor RAS over >or= 4 months unresponsive to topical corticosteroids. Patients were randomly assigned to one of three study groups: blind therapy with systemic sulodexide or systemic prednisone and control (no treatment). The outcomes were assessed blind on the basis of the days to recovery from pain and days to recovery from ulceration (epithelialization) during the first month of therapy; the number of aphthae appearing during the second month of therapy; and the number of aphthae appearing in the 2 months after the end of the 2-month treatment cycle.\n The effectiveness of systemic sulodexide was almost comparable with that of systemic prednisone in patients with frequent RAS, without significant adverse effects.", "In an attempt to evaluate the efficacy of different methods of interventions to improve the appropriate use of drugs for acute diarrhoea, a controlled study has been carried out in 6 districts in Yogyakarta and Central Java provinces, Indonesia. This study was designed to investigate the impacts of two different methods of educational intervention, i.e. a small group face-to-face intervention and a formal seminar for prescribers, on prescribing practice in acute diarrhoea. The districts were randomly assigned into 3 groups and 15 health centers were selected from each district. Prescribers in Group 1 underwent a small group face-to-face intervention conducted in the respective health center. Those in Group 2 attended a formal seminar conducted at the district level. Prescribers in Group 3 served as the control group. Both interventions were given on a single occasion without follow-up supervision or monitoring. Written information materials on the appropriate management of acute diarrhoea were developed and were provided to all prescribers in the intervention groups. Focus group discussions (FGDs) involving prescribers and consumers in the 6 districts were carried out to identify various underlying motivations of drug use in acute diarrhoea. The findings of the FGDs were used as part of the intervention materials. To evaluate the impacts of these interventions on prescribing practice, a prescribing survey for patients under five years old with acute diarrhoea was carried out in health centers covering 3-month periods before and after the intervention. The results showed that both interventions were equally effective in improving the levels of knowledge of prescribers about the appropriate management of acute diarrhoea. They were also partially effective in improving the appropriate use of drugs, reducing the use of non-rehydration medications. There was a highly significant reduction of antimicrobial usage either after small-group face-to-face intervention (77.4 +/- 2.7% to 60.4 +/- 2.9%; P < 0.001) or formal seminar (82.3 +/- 3.0% to 72.3 +/- 3.6%; P < 0.001), and the former caused significantly (P < 0.001) greater reduction than the latter. There was also a significant (P < 0.01) reduction in the usage of antidiarrhoeals after both interventions, i.e. from 20.3 +/- 3.7% to 12.5 +/- 3.3% (P < 0.01) after face-to-face intervention and from 48.5 +/- 4.1% to 27.0 +/- 4.3% (P < 0.01) after seminar. However, the formal seminar had a significantly (P < 0.01) greater impact than the small group face-to-face intervention. There was also a trend toward increased oral rehydration solution (ORS) usage after both interventions, but this did not achieve the level of statistical significance (P > 0.05). No changes were observed in the control group. Although the small group face-to-face intervention did not appear to offer greater impacts over large seminars in improving the appropriate use of drugs in acute diarrhoea, since the unit cost of training is far less costly than the seminar, it might be feasibly implemented in the existing supervisory structure of the health system.", "A gap exists between evidence and practice regarding the management of cardiovascular risk factors. This gap could be narrowed if systematically developed clinical practice guidelines were effectively implemented in clinical practice. We evaluated the effects of a tailored intervention to support the implementation of systematically developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease.\n We conducted a cluster-randomized trial comparing a tailored intervention to passive dissemination of guidelines in 146 general practices in two geographical areas in Norway. Each practice was randomized to either the tailored intervention (70 practices; 257 physicians) or control group (69 practices; 244 physicians). Patients started on medication for hypertension or hypercholesterolemia during the study period and all patients already on treatment that consulted their physician during the trial were included. A multifaceted intervention was tailored to address identified barriers to change. Key components were an educational outreach visit with audit and feedback, and computerized reminders linked to the medical record system. Pharmacists conducted the visits. Outcomes were measured for all eligible patients seen in the participating practices during 1 y before and after the intervention. The main outcomes were the proportions of (1) first-time prescriptions for hypertension where thiazides were prescribed, (2) patients assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs, and (3) patients treated for hypertension or hypercholesterolemia for 3 mo or more who had achieved recommended treatment goals. The intervention led to an increase in adherence to guideline recommendations on choice of antihypertensive drug. Thiazides were prescribed to 17% of patients in the intervention group versus 11% in the control group (relative risk 1.94; 95% confidence interval 1.49-2.49, adjusted for baseline differences and clustering effect). Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals.\n Our tailored intervention had a significant impact on prescribing of antihypertensive drugs, but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care.", "The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained.", "Community pharmacists have increasing involvement in the self-management of minor illness as a result of the availability of a wider range of over-the-counter (OTC) medicines. We undertook a randomized controlled trial (RCT) to assess the effectiveness and efficiency of educational strategies to implement evidence-based guidelines for the sale of OTC anti-fungals in the community pharmacy setting.\n The aim of the study was to compare the effectiveness and efficiency of two guideline dissemination strategies in community pharmacy settings.\n A 2 x 2 factorial, cluster RCT was conducted with 60 community pharmacies in the Grampian region of Scotland. The interventions included dissemination of an evidence-based guideline for OTC management of vulvovaginal candidiasis (thrush) by postal dissemination (control), educational outreach visit or attendance at a continuing professional education session. Pre- and post-intervention simulated patient visits were made to participating pharmacies. The simulated patients completed assessment forms following each visit. The primary outcome was the appropriateness (based upon the guidelines) of sale or no sale of OTC anti-fungals.\n There were no significant differences in the proportion of appropriate outcomes following educational outreach [odds ratio (OR) = 1.1; 95% confidence interval (CI) 0.52 to 2.45] or continuing professional education (OR = 0.88; 95% CI 0.41 to 1.91).\n Neither strategy was effective in improving the appropriateness of OTC management of vulvovaginal candidiasis by community pharmacy staff. Further research is needed to identify barriers to guideline implementation and evidence-based practice in this setting.", "Maintaining greater than 95% adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection. Furthermore, evidence suggests that adherence rates of between 70% and 89% are significantly associated with viral rebound and the development of drug resistance. Adherence rates at and above the 95% level are difficult for patients to achieve and maintain. Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital. The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices designed to assist patient memory and adherence. A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems. Adherence was assessed using patient self-report over the past 4, 7, and 28 days and by calculation of the Morisky score. The study was conducted as a randomised controlled trial using the stepped wedge design with a total of 68 subjects randomised to receive the intervention over a 20-week period. Adherence before and after the intervention formed the analysis. There was a significant decrease in the number of missed doses over the past 4 (1.9 to 1.0, p < 0.001), 7 (3.0 to 1.8, p < 0.001) and 28 (7.4 to 4.2, p < 0.001) days and a decrease in the Morisky score, indicating an improvement in medication taking behaviour (1.3 to 0.5 p < 0.001).", "Quality improvement initiatives in health services rely upon the effective introduction of clinical practice guidelines. However, even well constructed guidelines have little effect unless supported by dissemination and implementation strategies.\n To test the effectiveness of 'educational outreach' as a strategy for facilitating the uptake of dyspepsia management guidelines in primary care.\n A pragmatic, cluster-randomised controlled trial of guideline introduction, comparing educational outreach with postal guideline dissemination alone.\n One-hundred and fourteen general practices (233 general practitioners) in the Salford and Trafford Health authority catchment area in the northwest of England.\n All practices received guidelines by post in July 1997. The intervention group practices began to receive educational outreach three months later. This consisted of practice-based seminars with hospital specialists at which guideline recommendations were appraised, and implementation plans formulated. Seminars were followed up with 'reinforcement' visits after a further 12 weeks. Outcome measures were: (a) the appropriateness of referral for; and (b) findings at, open access upper gastrointestinal endoscopy; (c) costs of GP prescriptions for acid-suppressing drugs, and (d) the use of laboratory-based serological tests for Helicobacter pylori. Data were collected for seven months before and/or after the intervention and analysed by intention-to-treat.\n (a) The proportion of appropriate referrals was higher in the intervention group in the six-month post-intervention period (practice medians: control = 50.0%, intervention = 63.9%, P < 0.05); (b) the proportion of major findings at endoscopy did not alter significantly; (c) there was a greater rise in overall expenditure on acid-suppressing drugs in the intervention as compared with the control group (+8% versus +2%, P = 0.005); and (d) the median testing rate per practice for H pylori in the post-intervention period was significantly greater in the intervention group (four versus O, P < 0.001).\n This study suggests that educational outreach may be more effective than passive guideline dissemination in changing clinical behaviour. It also demonstrates that unpredictable and unanticipated outcomes may emerge.", "To assess the effectiveness of a multifaceted intervention to improve the management of glucocorticoid-induced osteoporosis (GIOP).\n Of 21 rheumatologists, 11 were randomly assigned to a 3-part intervention consisting of a lecture and discussion regarding optimal management of GIOP, a confidential doctor-specific audit regarding management of GIOP, and a reminder mailing including concise pharmacologic recommendations. The remaining 10 rheumatologists received no special education. Patients with rheumatoid arthritis (RA) taking oral glucocorticoids seen in the 2 months after the intervention were followed for 6 months. Medical records were assessed to determine the proportion undergoing bone mineral density testing or receiving pharmacologic interventions for GIOP during the 6 months before and 6 months after the intervention.\n There were 373 patients with RA taking oral glucocorticoids whose records were assessed. Patients in both arms of the trial were similar with respect to age, sex, menopausal status, glucocorticoid dosage and duration, duration of RA, disease-modifying antirheumatic drug use, and the proportion with comorbid conditions. At baseline, there was no significant difference between the patients with respect to osteoporosis medication use (intervention 32% versus control 34%) or bone densitometry use (intervention 9% versus control 5%). After the intervention and a 6-month followup period, there were no differences in treatment (intervention 33% versus control 38%) or bone densitometry use (intervention 8% versus control 8%). Adjusting for patient and physician characteristics did not significantly change these results.\n A multifaceted intervention for GIOP, including doctor education, practice audit, and treatment suggestions, had no significant benefit on testing or treatment by rheumatologists over a 6-month followup period. Other intervention approaches need to be tested." ]

[ "10929921", "11399700", "21255253", "8414777", "21464382", "19434268", "17687129", "12475845", "18179756" ]

[ "Primary prevention of acute respiratory tract infections in children using a bacterial immunostimulant: a double-masked, placebo-controlled clinical trial.", "Safety and efficacy of two courses of OM-85 BV in the prevention of respiratory tract infections in children during 12 months.", "A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study).", "Stimulation of nonspecific immunity to reduce the risk of recurrent infections in children attending day-care centers. The Epicrèche Research Group.", "A randomized controlled trial of home injury hazard reduction: the HOME injury study.", "Management for the children with otitis media with effusion in the tertiary hospital.", "Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.", "Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study.", "Intranasal flunisolide treatment in children with adenoidal hypertrophy." ]

[ "Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV has shown some protective effect for ARTIs in preschool children and a reduction in exacerbations of chronic bronchitis in adults.\n This trial reports results of a double-masked, placebo-controlled, parallel-group clinical study that assessed the efficacy and tolerability of OM-85 BV in the prevention of ARTIs in school girls living in an orphanage.\n Two hundred girls (age range, 6 to 13 years) living in an orphanage entered the trial. Participants were randomly allocated to receive either OM-85 BV or placebo for 10 consecutive days a month for 3 consecutive months. Patients were followed up for 6 months, including the administration period. The trial began in September 1996 and finished in March 1997. Primary end points were the type and number of infections. Secondary end points included when an infection occurred, time to clinical cure, severity of infection, absenteeism from school due to an ARTI, number of antibiotics or other drugs prescribed, and duration of concomitant drug treatment.\n During the trial, patients in the OM-85 BV group experienced 143 ARTIs (135 upper ARTIs and 8 otitis episodes) and patients in the placebo group experienced 299 ARTIs (273 upper ARTIs, 1 lower ARTI, and 25 otitis episodes). The median number of ARTIs was 1.0 (0.0, 3.0; 5th percentile, 95th percentile) in the OM-85 BV group compared with 3.0 (2.0, 4.0; 5th percentile, 95th percentile) in the placebo group. This difference was statistically significant (P < 0.001). Participants who received OM-85 BV also showed significantly better results (P < 0.001) than participants who received placebo in terms of median duration of illness, median number of missed school days due to an ARTI, median number of antibiotic and drug courses, and median duration of concomitant treatment. There were significant differences (P < 0.05) in severity of ARTIs during month 4 of the trial, with patients receiving OM-85 BV showing less severe ARTIs than patients receiving placebo and shorter mean time to clinical cure from the second month to the fourth month. No adverse events related to the trial medications were reported. Conclusions: OM-85 BV had a preventive effect on ARTIs in the school girls, with a reduction in the antibiotic requirements and the duration of ARTIs. Future studies are needed to further explore the role of OM-85 BV in the prevention of ARTIs.", "Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV (bronchovaxom) has shown protective effect for ARTIs on children. We report a double-blind, placebo-controlled, parallel, prospective clinical trial to assess the safety and efficacy of two courses of OM-85 BV in the prevention of ARTIs in susceptible children during 12 months.\n Fifty-four susceptible children from 1 to 12 years of age living in the metropolitan area of Chihuahua City were selected. They were randomized to receive either OM-85 BV or placebo (one capsule a day for 10 days a month for 3 consecutive months) at the beginning of the trial and 6 months later with the same schedule. Patients were followed up for 12 months, including the administration period. The trial began in July 1997 and ended in April 1999.\n The number (mean +/- SD) of ARTIs was 5.04 +/- 1.99 (median, 5.0) in the OM-85 BV group vs 8.0 +/- 2.55 (median, 8.0) in the placebo group, with a mean difference of - 2.96 (95% confidence interval [CI], - 4.22 to - 1.7). The number of antibiotic courses was 2.46 +/- 2.08 (median, 1.5) in the treatment group vs 4.46 +/- 2.08 (median, 4.0) in the control group, a difference of - 2.0 (95% CI, - 3.14 to - 0.86). The total duration of ARTIs was 35.23 +/- 17.64 days (median, 30.5 days) in the OM-85 BV group vs 60.75 +/- 25.44 days (median, 55.0 days) in the placebo group, ie, a difference of - 25.52 days (95% CI, - 37.56 to - 13.47 days), p < 0.001 by Student's t test and Mann-Whitney U test for all the items. Four patients in the OM-85 BV group had five adverse events. Only one episode of skin rash was related to the medication intake. Six patients in the control group had six adverse events.\n OM-85 BV had a preventive effect on ARTI in the susceptible children for 12 months with an important reduction on the antibiotic requirements and the number of days of suffering ARTIs.", "Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients' well-being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and perception of well- of children with hemophilia.\n This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image-proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10-year time period.\n Forty-five children with severe hemophilia A, aged 1-7 years (median 4), with negative clinical-radiologic joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factor VIII (25 IU kg(-1) 3 × week) or episodic therapy with ≥25 IU kg(-1) every 12-24 h until complete clinical bleeding resolution. Safety, feasibility, direct costs and QoL were also evaluated.\n Twenty-one children were assigned to prophylaxis, 19 to episodic treatment. Children on prophylaxis had fewer hemarthroses than children on episodic therapy: 0.20 vs. 0.52 events per patient per month (P < 0.02). Plain-film radiology showed signs of arthropathy in six patients on prophylaxis (29%) vs. 14 on episodic treatment (74%) (P < 0.05). Prophylaxis was more effective when started early (≤36 months), with patients having fewer joint bleeds (0.12 joint bleeds per patient per month) and no radiologic signs of arthropathy.\n This randomized trial confirms the efficacy of prophylaxis in preventing bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life.\n © 2011 International Society on Thrombosis and Haemostasis.", "A randomized, double blind, placebo-controlled clinical trial was performed in 423 children attending day-care centers to assess whether stimulating nonspecific immunity would reduce the incidence of recurrent infections. The drug used for the trial (Imocur) is an extract obtained from eight different species of bacteria. At the end of the total follow-up period (3 months with treatment and 4.5 months without), the risk for > or = 4 episodes of upper respiratory infections was not significantly lower in the treated group than in the placebo group (26.7% vs. 33.8%, relative risk, 0.79; 95% confidence interval, 0.59 to 1.06). In an exploratory analysis limited to the 3-month treatment period, however, we observed a 48% reduction in the risk of presenting > or = 3 episodes of upper respiratory infections: 9.5% vs. 18.3%, respectively, in the treatment group and the placebo group (relative risk, 0.52; 95% confidence interval, 0.31 to 0.86). Similar results were found for the risk of > or = 1 episode of gastroenteritis. We also observed a strong correlation between the drug efficacy and age; this observation is coherent with the underlying pathophysiologic model in which the immune system matures with age.", "To test the efficacy of installing safety devices in the homes of young children on total injury rates and on injuries deemed a priori modifiable by the installation of these devices.\n A nested, prospective, randomized controlled trial.\n Indoor environment of housing units.\n Mothers and their children from birth to 3 years old participating in the Home Observation and Measures of the Environment study. Among 8878 prenatal patients, 1263 (14.2%) were eligible, 413 (32.7%) agreed to participate, and 355 were randomly assigned to the intervention (n = 181) or control (n = 174) groups.\n Installation of multiple passive measures (eg, stair gates, cabinet locks, and smoke detectors) to reduce exposure to injury hazards. Injury hazards were assessed at home visits by teams of trained research assistants using a validated survey.\n Modifiable and medically attended injury (ie, telephone calls, office visits, and emergency visits for injury).\n The mean age of children at intervention was 6.3 months. Injury hazards were reduced in the intervention homes but not in the control homes at 1 and 2 years (P < .004). There was no difference in the rate for all medically attended injuries in intervention children compared with controls: 14.3 injuries (95% confidence interval [CI], 9.7-21.1 injuries) vs 20.8 injuries (95% CI, 14.4-29.9 injuries) per 100 child-years (P = .17); but there was a significant reduction in the rate of modifiable medically attended injuries in intervention children compared with controls: 2.3 injuries (95% CI, 1.0-5.5 injuries) vs 7.7 injuries (95% CI, 4.2-14.2 injuries) per 100 child-years (P = .03).\n An intervention to reduce exposure to hazards in homes led to a 70% reduction in the rate of modifiable medically attended injury.\n clinicaltrials.gov Identifier: NCT00129324.", "Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.\n Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.\n Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).\n In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.", "Effective ways to prevent arthropathy in severe hemophilia are unknown.\n We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI).\n Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups.\n Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "Recurrent upper respiratory tract infections (URTIs) are common illnesses in young children. As the immunoactive bacterial extract OM-85 has been shown to prevent these infections in both adults and children, the aim of the present trial was to investigate further its efficacy and safety in infection-prone children.\n This is a randomized, double-blind, placebo-controlled, multicenter study with OM-85 in 232 patients aged 36 to 96 months with recurrent URTIs. Treatment was one capsule daily during month 1 and during 10 days in months 3 to 5. URTI was defined by the presence of at least two of the following: rhinitis, pharyngitis, cough, hoarseness, temperature > or = 38.5 degrees C, or URTI-related prescription of an antibiotic.\n OM-85-treated patients had a lower rate of URTIs (p < 0.05). The cumulated difference in URTIs between the two groups reached - 0.40 URTIs per patient in 6 months, corresponding to a 16% reduction in the active-treatment group with respect to placebo. The largest difference was observed in the patients having had three or more URTIs during the study period; odds ratios for three or more URTIs were 0.51 (95% confidence interval, 0.29 to 0.91) and 0.65 (95% confidence interval, 0.37 to 1.11) after 5 months and 6 months, respectively. The difference between OM-85 and placebo was independent of age but was more important in patients reporting a larger number of URTIs in the previous year. Patients' global assessment showed improvement in comparison to the previous season in the majority of the cases (OM-85, 78.4% of cases; placebo, 75.5%); however, there were more cases reporting worsening with placebo (6.4% vs 0.9%; p = 0.05).\n OM-85 treatment significantly reduced the rate of URTIs, particularly in children with a history of frequent URTIs. Safety and tolerance of test medication were good, comparable to placebo.", "Adenoidal hypertrophy (AH) represents one of the most frequent indications for surgery in children and it has been proposed that treatment with intranasal corticosteroids can decrease the size of AH. Therefore, the aim of the study is to evaluate the effect of the use of intranasal flunisolide among children affected by AH. 178 children with AH were evaluated in this randomised and controlled study. Inclusion criteria for the study required that each patient had to have a III or IV degree of AH on the initial endoscopic examination. Children were treated with intranasal flunisolide or isotonic saline solution for 8 weeks. After treatment, endoscopy was performed to re-evaluate AH degree. Flunisolide treatment was associated with significant (p less than 0.04) reduction of AH degree. There was moreover a consistent reduction of children (46 out of 58) proposed to adenoidectomy. No clinically important adverse events were reported. In conclusion, this preliminary study demonstrates that an 8-week treatment with intranasal flunisolide is significantly associated with reduction of AH, thus preventing the recurrence to adenoidectomy, and is safe." ]

[ "15294086", "16770291", "17891043", "15751766", "21457056", "18676516", "20163349", "15659884", "19549342" ]

[ "Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention.", "Home visits to improve adherence to highly active antiretroviral therapy: a randomized controlled trial.", "Telephone support to improve antiretroviral medication adherence: a multisite, randomized controlled trial.", "A randomized controlled trial to enhance antiretroviral therapy adherence in patients with a history of alcohol problems.", "Brief behavioral self-regulation counseling for HIV treatment adherence delivered by cell phone: an initial test of concept trial.", "A video game improves behavioral outcomes in adolescents and young adults with cancer: a randomized trial.", "Results of a community-based antiretroviral treatment program for HIV-1 infection in Western Uganda.", "Multidisciplinary HIV adherence intervention: a randomized study.", "Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial." ]

[ "Adherence to combination antiretroviral therapy (ART) has been shown to be a determining factor in controlling viral replication, maintaining immunologic function and long-term survival in HIV-positive individuals. Little information is available on strategies to improve adherence in pediatric HIV-infected patients. We conducted a randomized, nonblinded, pilot study to determine if a home-based nursing intervention would improve medication adherence. The study was offered to all eligible HIV-positive patients receiving care at Connecticut Children's Medical Center's (CCMC) Pediatric and Youth HIV Program. Sixty-seven percent (37/55) of the patients and their caretakers participated. We randomized participants to either standard of care or the intervention trial. The intervention was designed to improve knowledge and understanding of HIV infection and HIV medications and to resolve or modify barriers to adherence. Both groups completed pre- and post-intervention questionnaires, assessing their knowledge and understanding of HIV, ART, and adherence. Adherence was estimated objectively from medication refill history and subjectively from a self-report score. We also inferred adherence from pre- to post-test plasma viral load and CD4+ T-cell percentages. The knowledge score (p = 0.02) and medication refill history (p = 0.002) improved significantly in the intervention group. The adherence self-report score improved, although not significantly (p = 0.07). We did not observe statistical differences in CD4+ T-cell counts or viral load between groups. We conclude that our home-based nursing intervention helped HIV-positive children and their families in better adhering to prescribed medication regimens.", "Few rigorously designed studies have documented the efficacy of interventions to improve medication adherence among patients prescribed highly active antiretroviral. Data are needed to justify the use of limited resources for these programs.\n A 2-arm, randomized, controlled trial evaluated the efficacy of a community-based, home-visit intervention to improve medication adherence. Participants were 171 HIV-infected adults prescribed a minimum of 3 antiretroviral agents. The majority had a past or current history of substance abuse. Subjects were randomly assigned to receive home visits for 1 year or usual care. Medication adherence was assessed with Medication Event Monitoring stem caps at 3-month intervals from randomization through 3 months after the conclusion of the intervention.\n A larger proportion of subjects in the intervention group demonstrated adherence greater than 90% compared with the control group at each time point after baseline. The difference over time was statistically significant (Extended Mantel-Haenszel test: 5.80, P = 0.02). A statistically significant intervention effect on HIV-RNA level or CD4 cell count was not seen, but there was a statistically significant association between greater than 90% adherence and an undetectable HIV-RNA over time (P < 0.03).\n Home visits from a nurse and a community worker were associated with medication adherence greater than 90% among a cohort of socially vulnerable people living with HIV/AIDS in northeastern United States.", "To determine whether proactive telephone support improves adherence to antiretroviral therapy (ART) and clinical outcomes when compared to standard care.\n A multisite, randomized controlled trial (RCT) was conducted with 109 ART-naive subjects coenrolled in AIDS Clinical Trials Group (ACTG) 384. Subjects received standard clinic-based patient education (SC) or SC plus structured proactive telephone calls. The customized calls were conducted from a central site over 16 weeks by trained registered nurses. Outcome measures (collected over 64 weeks) included an ACTG adherence questionnaire and 384 study endpoints.\n For the primary endpoint, self-reported adherence, a significantly better overall treatment effect was observed in the telephone group (P = 0.023). In a post hoc analysis, composite adherence scores, taken as the first 2 factor scores from a principal components analysis, also found significant intervention benefit (P = 0.023 and 0.019 respectively). For the 384 primary study endpoint, time to regimen failure, the Kaplan-Meier survival curve for the telephone group remained above the SC group at weeks 20 to 64; a Cox proportional hazard model that controlled for baseline RNA stratification, CD4, gender, age, race/ethnicity, and randomized ART treatment arm suggested the telephone group tended to have a lower risk for failure (hazard ratio = 0.68; 95% confidence interval: 0.38 to 1.23).\n Findings indicate that customized, proactive telephone calls have good potential to improve long-term adherence behavior and clinical outcomes.", "To assess the effectiveness of an individualized multicomponent intervention to promote adherence to antiretroviral therapy (ART) in a cohort of HIV-infected individuals with a history of alcohol problems.\n We conducted a randomized controlled trial to compare the usual medical follow-up with an adherence intervention.\n The principal enrolment site was Boston Medical Center, a private, not-for-profit, academic medical institution.\n HIV-infected patients with a history of alcohol problems on ART. A total of 151 were enrolled and 141 (93%) were assessed at follow-up. Intervention: A nurse, trained in motivational interviewing, completed the following over 3 months in four encounters: addressed alcohol problems; provided a watch with a programmable timer to facilitate pill taking; enhanced perception of treatment efficacy; and delivered individually tailored assistance to facilitate medication use.\n Prior 30-day adherence > or =95%, prior 3-day adherence of 100%, CD4 cell count, HIV RNA and alcohol consumption, each at both short- and long-term follow-up.\n At follow-up, no significant differences in medication adherence, CD4 cell count, HIV RNA or alcohol consumption were found (all P values >0.25).\n A multicomponent intervention to enhance adherence among HIV-infected individuals with a history of alcohol problems was not associated with changes in medication adherence, alcohol consumption or markers of HIV disease progression. The failure to change adherence in a group at high risk for poor adherence, despite utilizing an intensive individual-focused patient intervention, supports the idea of addressing medication adherence with supervised medication delivery or markedly simplified dosing regimens.", "Affordable and effective antiretroviral therapy (ART) adherence interventions are needed for many patients to promote positive treatment outcomes and prevent viral resistance. We conducted a two-arm randomized trial (n = 40 men and women receiving and less than 95% adherent to ART) to test a single office session followed by four biweekly cell phone counseling sessions that were grounded in behavioral self-management model of medication adherence using data from phone-based unannounced pill counts to provide feedback-guided adherence strategies. The control condition received usual care and matched office and cell phone/pill count contacts. Participants were baseline assessed and followed with biweekly unannounced pill counts and 4-month from baseline computerized interviews (39/40 retained). Results showed that the self-regulation counseling delivered by cell phone demonstrated significant improvements in adherence compared to the control condition; adherence improved from 87% of pills taken at baseline to 94% adherence 4 months after baseline, p < 0.01. The observed effect sizes ranged from moderate (d = 0.45) to large (d = 0.80). Gains in adherence were paralleled with increased self-efficacy (p < 0.05) and use of behavioral strategies for ART adherence (p < 0.05). We conclude that the outcomes from this test of concept trial warrant further research on cell phone-delivered self-regulation counseling in a larger and more rigorous trial.", "Suboptimal adherence to self-administered medications is a common problem. The purpose of this study was to determine the effectiveness of a video-game intervention for improving adherence and other behavioral outcomes for adolescents and young adults with malignancies including acute leukemia, lymphoma, and soft-tissue sarcoma.\n A randomized trial with baseline and 1- and 3-month assessments was conducted from 2004 to 2005 at 34 medical centers in the United States, Canada, and Australia. A total of 375 male and female patients who were 13 to 29 years old, had an initial or relapse diagnosis of a malignancy, and currently undergoing treatment and expected to continue treatment for at least 4 months from baseline assessment were randomly assigned to the intervention or control group. The intervention was a video game that addressed issues of cancer treatment and care for teenagers and young adults. Outcome measures included adherence, self-efficacy, knowledge, control, stress, and quality of life. For patients who were prescribed prophylactic antibiotics, adherence to trimethoprim-sulfamethoxazole was tracked by electronic pill-monitoring devices (n = 200). Adherence to 6-mercaptopurine was assessed through serum metabolite assays (n = 54).\n Adherence to trimethoprim-sulfamethoxazole and 6-mercaptopurine was greater in the intervention group. Self-efficacy and knowledge also increased in the intervention group compared with the control group. The intervention did not affect self-report measures of adherence, stress, control, or quality of life.\n The video-game intervention significantly improved treatment adherence and indicators of cancer-related self-efficacy and knowledge in adolescents and young adults who were undergoing cancer therapy. The findings support current efforts to develop effective video-game interventions for education and training in health care.", "To compare the treatment outcomes and mortality in a rural community-based ART (CBART) program with a hospital-based ART program in the same district.\n The study design was a non-randomized cohort study consisting of 185 persons living with HIV (PLWHIV) in the CBART cohort and 200 PLWHIV in the hospital cohort. Eligibility for both cohorts was: being HIV-infected and eligible for ART, being treatment naïve, age 18 years or older, and being a resident of Rwimi sub-county. The intervention consisted of a community-based program which included weekly home visits to patients by trained volunteers who delivered antiretroviral drugs (ARVs), monitored and supported adherence to treatment, and identified and reported adverse reactions and other clinical symptoms. Outcome variables were compared to patients in a hospital-based cohort who received the standard care delivered to all other HIV patients in the hospital. The main outcome measures were HIV-1 RNA viral load (VL), CD4 cell count and mortality after six months of treatment.\n Successful ART treatment outcome as measured by virological suppression (VL<400 copies/ml) in the CBART cohort were similar to those in the hospital-based cohort (90.1% vs 89.3%, p=0.47). The median CD4 cell count increased significantly in both cohorts (community-based cohort 159 cells/microl vs 145 cells/microl in the hospital-based cohort). Mortality was not significantly different in both cohorts (community-based cohort 11.9%, hospital-based cohort 9.0%).\n The findings show that outcomes of a CBART intervention in a rural area compare favorably to outcomes of hospital-based care. If the study results are sustainable over a longer time period, this model could be considered for ART roll-out to impoverished rural/remote populations in Uganda and elsewhere.", "Maintaining greater than 95% adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection. Furthermore, evidence suggests that adherence rates of between 70% and 89% are significantly associated with viral rebound and the development of drug resistance. Adherence rates at and above the 95% level are difficult for patients to achieve and maintain. Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital. The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices designed to assist patient memory and adherence. A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems. Adherence was assessed using patient self-report over the past 4, 7, and 28 days and by calculation of the Morisky score. The study was conducted as a randomised controlled trial using the stepped wedge design with a total of 68 subjects randomised to receive the intervention over a 20-week period. Adherence before and after the intervention formed the analysis. There was a significant decrease in the number of missed doses over the past 4 (1.9 to 1.0, p < 0.001), 7 (3.0 to 1.8, p < 0.001) and 28 (7.4 to 4.2, p < 0.001) days and a decrease in the Morisky score, indicating an improvement in medication taking behaviour (1.3 to 0.5 p < 0.001).", "As highly active antiretroviral therapy (HAART) becomes increasingly available to African children, it is important to evaluate simple and feasible methods of improving adherence in order to maximize benefits of therapy.\n HIV-1-infected children initiating World Health Organization non-nucleoside reverse transcriptase-inhibitor-containing first-line HAART regimens were randomized to use medication diaries plus counselling, or counselling only (the control arm of the study). The diaries were completed daily by caregivers of children randomized to the diary and counselling arm for nine months. HIV-1 RNA, CD4+ T cell count, and z-scores for weight-for-age, height-for-age and weight-for-height were measured at a baseline and every three to six months. Self-reported adherence was assessed by questionnaires for nine months.\n Ninety HIV-1-infected children initiated HAART, and were followed for a median of 15 months (interquartile range: 2-21). Mean CD4 percentage was 17.2% in the diary arm versus 16.3% in the control arm at six months (p = 0.92), and 17.6% versus 18.9% at 15 months (p = 0.36). Virologic response with HIV-1 RNA of <100 copies/ml at nine months was similar between the two arms (50% for the diary arm and 36% for the control, p = 0.83). The weight-for-age, height-for-age and weight-for-height at three, nine and 15 months after HAART initiation were similar between arms. A trend towards lower self-reported adherence was observed in the diary versus the control arm (85% versus 92%, p = 0.08).\n Medication diaries did not improve clinical and virologic response to HAART over a 15-month period. Children had good adherence and clinical response without additional interventions. This suggests that paediatric HAART with conventional counselling can be a successful approach. Further studies on targeted approaches for non-adherent children will be important." ]

[ "11832254", "17196274", "17880478", "314119", "10069785", "17767899", "10092561", "2271343", "15718182" ]

[ "Guideline-based early rehabilitation after myocardial infarction. A pragmatic randomised controlled trial.", "Home-based versus hospital-based rehabilitation after myocardial infarction: A randomized trial with preference arms--Cornwall Heart Attack Rehabilitation Management Study (CHARMS).", "A nurse-led cardiac rehabilitation programme improves health behaviours and cardiac physiological risk parameters: evidence from Chengdu, China.", "Brief group therapy in myocardial infarction rehabilitation: three- to four-year follow-up of a controlled trial.", "Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcome.", "The Birmingham Rehabilitation Uptake Maximisation Study (BRUM). Home-based compared with hospital-based cardiac rehabilitation in a multi-ethnic population: cost-effectiveness and patient adherence.", "Changes in cardiorespiratory fitness, psychological wellbeing, quality of life, and vocational status following a 12 month cardiac exercise rehabilitation programme.", "A controlled trial of community based coronary rehabilitation.", "Randomised controlled trial of cardiac rehabilitation in elderly patients with heart failure." ]

[ "To determine the effectiveness of individualised educational behavioural treatment delivered by cardiac nurses in hospital compared to usual care for patients following acute myocardial infarction.\n One hundred and fourteen consecutive patients were randomised to receive the intervention or usual care. Outcome assessment was by self-report questionnaire (the Hospital Anxiety and Depression Scale and Dartmouth COOP Health Status), interview at 1 month, and self-report at 3 and 12 months. The primary outcome was improvement in the Dartmouth COOP total score from baseline to 3 months.\n Four patients needed to be treated to give an additional patient with improvement in health status at 3 months (number needed to treat [NNT] 4, 95% confidence intervals [CIs] 3 to 12). The intervention group were more confident about returning to activities 1 month after discharge from hospital. Treated patients had fewer further treatment needs.\n An individualised educational behavioural treatment delivered by cardiac nurses in hospital may have substantial benefits. A large-scale pragmatic RCT is needed.", "Participation in cardiac rehabilitation after acute myocardial infarction is sub-optimal. Offering home-based rehabilitation may improve uptake. We report the first randomized study of cardiac rehabilitation to include patient preference.\n To compare the clinical effectiveness of a home-based rehabilitation with hospital-based rehabilitation after myocardial infarction and to determine whether patient choice affects clinical outcomes.\n Pragmatic randomized controlled trial with patient preference arms.\n Rural South West England.\n Patients admitted with uncomplicated myocardial infarction were offered hospital-based rehabilitation classes over 8-10 weeks or a self-help package of six weeks' duration (the Heart Manual) supported by a nurse. Primary outcomes at 9 months were mean depression and anxiety scores on the Hospital Anxiety Depression scale, quality of life after myocardial infarction (MacNew) score and serum total cholesterol.\n Of the 230 patients who agreed to participate, 104 (45%) consented to randomization and 126 (55%) chose their rehabilitation programme. Nine month follow-up data were available for 84/104 (81%) randomized and 100/126 (79%) preference patients. At follow-up no difference was seen in the change in mean depression scores between the randomized home and hospital-based groups (mean difference: 0; 95% confidence interval, -1.12 to 1.12) nor mean anxiety score (-0.07; -1.42 to 1.28), mean global MacNew score (0.14; -0.35 to 0.62) and mean total cholesterol levels (-0.18; -0.62 to 0.27). Neither were there any significant differences in outcomes between the preference groups.\n Home-based cardiac rehabilitation with the Heart Manual was as effective as hospital-based rehabilitation for patients after myocardial infarction. Choosing a rehabilitation programme did not significantly affect clinical outcomes.", "The aim of this study was to examine the effect of a cardiac rehabilitation programme on health behaviours and physiological risk parameters in patients with coronary heart disease in Chengdu, China.\n Epidemiological studies indicate a dose-, level- and duration-dependent relationship exists between cardiac behavioural and physiological risks and coronary heart disease incidence as well as subsequent cardiac morbidity and mortality. Cardiac risk factor modification has become the very primary goal of modern cardiac rehabilitation programmes.\n A randomized controlled trial was conducted. Coronary heart disease patients (n = 167) who met the sampling criteria in two tertiary medical centres in Chengdu, south-west China, were randomly assigned to either an intervention group (the cardiac rehabilitation programme) or control group (the routine care). The change of health behaviours (walking performance, step II diet adherence, medication adherence, smoking cessation) and physiological risk parameters (serum lipids, blood pressure, body weight) were assessed to evaluate the programme effect.\n Patients in the intervention group demonstrated a significantly better performance in walking, step II diet adherence, medication adherence; a significantly greater reduction in serum lipids including triglyceride, total cholesterol, low-density lipoprotein; and significantly better control of systolic and diastolic blood pressure at three months. The majority of these positive impacts were maintained at six months. The effect of the programme on smoking cessation, body weight, serum high-density lipoprotein, was not confirmed.\n A cardiac rehabilitation programme led by a nurse can significantly improve the health behaviours and cardiac physiological risk parameters in coronary heart disease patients. Nurses can fill significant treatment gaps in the risk factor management of patients with coronary heart disease.\n This study raises attention regarding the important roles nurses can play in cardiac rehabilitation and the unique way for nurses to meet the rehabilitative care needs of coronary heart disease patients. Furthermore, the hospital-home bridging nature of the programme also created a model for interfacing the acute care and community rehabilitative care.", "A trial of brief group therapy as part of a rehabilitation program for postmyocardial infarction (MI) patients was carried out. Forty-four patients surviving their first MI were randomly allocated to either group therapy or control group status and were followed over 4 years. An additional group of 17 patients were referred for post-MI group therapy sessions after the termination of the controlled experiment and were followed for 3 years. Patients who received group therapy had significantly less follow-up coronary morbidity and mortality, and returned to work at significant higher percentages than control patients. Although neither group therapy nor control group patients meaningfully altered conventional coronary risk factors, group therapy patients (in the controlled trial) successfully altered selected coronary-prone behaviors. Educational information regarding the physiological and psychological aspects of coronary heart disease, presented in the group therapy sessions, was forgotten over follow-up. It is concluded that the supportive aspects of the group therapy experience played the most important role in determining the rehabilitation advantages seen for treatment patients.", "It is still a matter of debate whether exercise training (ET) is a beneficial treatment in chronic heart failure (CHF).\n To determine whether long-term moderate ET improves functional capacity and quality of life in patients with CHF and whether these effects translate into a favorable outcome, 110 patients with stable CHF were initially recruited, and 99 (59+/-14 years of age; 88 men and 11 women) were randomized into 2 groups. One group (group T, n=50) underwent ET at 60% of peak &f1;O2, initially 3 times a week for 8 weeks, then twice a week for 1 year. Another group (group NT, n=49) did not exercise. At baseline and at months 2 and 14, all patients underwent a cardiopulmonary exercise test, while 74 patients (37 in group T and 37 in group NT) with ischemic heart disease underwent myocardial scintigraphy. Quality of life was assessed by questionnaire. Ninety-four patients completed the protocol (48 in group T and 46 in group NT). Changes were observed only in patients in group T. Both peak &f1;O2 and thallium activity score improved at 2 months (18% and 24%, respectively; P<0. 001 for both) and did not change further after 1 year. Quality of life also improved and paralleled peak VO2. Exercise training was associated both with lower mortality (n=9 versus n=20 for those with training versus those without; relative risk (RR)=0.37; 95% CI, 0.17 to 0.84; P=0.01) and hospital readmission for heart failure (5 versus 14; RR=0.29; 95% CI, 0.11 to 0.88; P=0.02). Independent predictors of events were ventilatory threshold at baseline (beta-coefficient=0.378) and posttraining thallium activity score (beta-coefficient -0.165).\n Long-term moderate ET determines a sustained improvement in functional capacity and quality of life in patients with CHF. This benefit seems to translate into a favorable outcome.", "To evaluate the relative effectiveness and cost-effectiveness of a home-based programme of cardiac rehabilitation using the Heart Manual, with centre-based programmes. It also sought to explore the reasons for non-adherence to cardiac rehabilitation programmes.\n An individually randomised trial, with minimisation for age, gender, ethnicity, initial diagnosis and hospital of recruitment. Participants were followed up after 6, 12 and 24 months by questionnaire and clinical assessment. Individual semistructured interviews were undertaken in the homes of a purposive sample of patients who did not adhere to their allocated programme, and focus groups were undertaken with groups of patients who adhered to the programmes.\n Four hospitals in predominantly inner-city, multi-ethnic, socio-economically deprived areas of the West Midlands in England, for 2 years from 1 February 2002.\n A total of 525 patients who had experienced a myocardial infarction (MI) or coronary revascularisation within the previous 12 weeks.\n All the rehabilitation programmes included exercise, relaxation, education and lifestyle counselling. All patients were seen by a cardiac rehabilitation nurse prior to hospital discharge and provided with information about their condition and counselling about risk factor modification. The four centre-based programmes varied in length from nine sessions at weekly intervals of education, relaxation and circuit training to 24 individualised sessions over 12 weeks of mainly walking, fixed cycling and rowing with group-based education. The home-based programme consisted of an appropriate version of the Heart Manual, home visits and telephone contact. The Heart Manual was introduced to patients on an individual basis, either in hospital or on a home visit. Home visits by a nurse took place at approximately 1, 6 and 12 weeks after recruitment, with a telephone call at 3 weeks. At the final visit, patients were encouraged to maintain their lifestyle changes and to continue with their exercise programme. Where needed, follow-up was made by a rehabilitation nurse who spoke Punjabi. An audiotape of an abridged version of the Heart Manual in Punjabi accompanied the manual for patients with a limited command of English.\n Primary outcomes were smoking cessation, blood pressure, total and high-density lipoprotein cholesterol, exercise capacity measured by the incremental shuttle walking test and psychological status measured by the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included self-reported diet, physical activity, cardiac symptoms and quality of life. Health service resource use and costs of rehabilitation programmes from health service and societal perspectives were also measured. Adherence to the physical activity element of the rehabilitation programmes was measured by questionnaire 6, 9 and 12 weeks.\n No clinically or statistically significant differences were found in any of the primary or secondary outcome measures between the home- and centre-based groups. Significant improvements in total cholesterol, smoking prevalence, the HADS anxiety score, self-reported physical activity and diet were seen in both arms between baseline and the 6-month follow-up. Five or more contacts with a cardiac rehabilitation nurse were received by 96% of home-based participants, whereas only 56% of centre-based participants attended this many rehabilitation classes. The direct rehabilitation costs to the health service were significantly higher for the home-based programme (mean cost 198 pounds versus 157 pounds for the centre-based programme), but when patient costs were included the mean cost of the centre-based arm rose to 182 pounds. Patients' reasons for not taking up or adhering to cardiac rehabilitation were multifactorial and very individual. Other health problems limited some patients' ability to exercise. Most non-adherers found some aspects of their cardiac rehabilitation programme helpful. Many had adapted advice on rehabilitation and were continuing to exercise in other ways and had made lifestyle changes, particularly to their diet. The home-based patients' lack of motivation to exercise on their own at home was a major factor in non-adherence. The focus groups revealed little diversity of views among patients from each programme. Patients in the hospital programme enjoyed the camaraderie of group exercise and the home-based patients valued the wealth of information and advice in the Heart Manual.\n A home-based cardiac rehabilitation programme for low- to moderate-risk patients does not produce inferior outcomes compared with the traditional centre-based programmes. With the level of home visiting in this trial, the home-based programme was more costly to the health service, but with the difference in costs borne by patients attending centre-based programmes. Different reasons were given by home and hospital cardiac rehabilitation patients for not taking up or adhering to cardiac rehabilitation, with home-based patients often citing a lack of motivation to exercise at home. Social characteristics, individual patient needs and the location of cardiac rehabilitation programmes need to be taken into account in programme design to maximise participation. Research is recommended into cardiac rehabilitation in patients from ethnic minority groups; measurement tools to assess physical activity and dietary change; evaluating the Heart Manual in patients who decline centre-based cardiac rehabilitation; the implementation of home-based programmes in the UK; and strategies that sustain physical activity in the long term.", "To examine and evaluate improvements in cardiorespiratory fitness, psychological wellbeing, quality of life, and vocational status in postmyocardial infarction patients during and after a comprehensive 12 month exercise rehabilitation programme.\n The sample population comprised 124 patients with a clinical diagnosis of myocardial infarction (122 men and two women).\n 62 patients were randomly allocated to a regular weekly aerobic training programme, three times a week for 12 months, and compared with 62 matched controls who did not receive any formal exercise training. A five year follow up questionnaire/interview was subsequently conducted on this population to determine selected vocational/lifestyle changes.\n Significant improvements in cardiorespiratory fitness (p < 0.01-0.001), psychological profiles (p < 0.05-0.001), and quality of life scores (p < 0.001) were recorded in the treatment population when compared with their matched controls. Although there were no significant differences in mortality, a larger percentage of the regular exercisers resumed full time employment and they returned to work earlier than the controls. Controls took lighter jobs, lost more time from work, and suffered more non-fatal reinfarctions (p < 0.05-0.01).\n Regularly supervised and prolonged aerobic exercise training improves cardiorespiratory fitness, psychological status, and quality of life. The trained population also had a reduction in morbidity following myocardial infarction, and significant improvement in vocational status over a five year follow up period.", "Two hundred patients who had suffered an acute myocardial infarction 4-6 weeks before entered a randomised controlled trial of exercise treatment at a community sports centre supervised by a general practitioner. Eighty one per cent of the treatment group continued to exercise until they returned to work and 73% completed three months' exercise. There were no serious complications of the exercise course. The prevalence of angina pectoris fell by 10% in the treatment group but rose by 60% in the control group. The perceived energy level rose by significantly more in the treatment group than in the controls. The rise in predicted maximum oxygen uptake was significantly greater in the treatment group than in the control group as was the reduction in the double product (a reflection of myocardial workload) at peak exercise. Coronary rehabilitation in the community can be both safe and effective.", "Heart failure, a condition predominantly affecting the elderly, represents an ever-increasing clinical and financial burden for the NHS. Cardiac rehabilitation, a service that incorporates patient education, exercise training and lifestyle modification, requires further evaluation in heart failure management.\n The aim of this study was to determine whether a cardiac rehabilitation programme improved on the outcomes of an outpatient heart failure clinic (standard care) for patients, over 60 years of age, with chronic heart failure.\n Two hundred patients (60-89 years, 66% male) with New York Heart Association (NYHA) II or III heart failure confirmed by echocardiography were randomised. Both standard care and experimental groups attended clinic with a cardiologist and specialist nurse every 8 weeks. Interventions included exercise prescription, education, dietetics, occupational therapy and psychosocial counselling. The main outcome measures were functional status (NYHA, 6-min walk), health-related quality of life (MLHF and EuroQol) and hospital admissions.\n There were significant improvements in MLHF and EuroQol scores, NYHA classification and 6-min walking distance (meters) at 24 weeks between the groups (p<0.001). The experimental group had fewer admissions (11 vs. 33, p<0.01) and spent fewer days in hospital (41 vs. 187, p<0.001).\n Cardiac rehabilitation, already widely established in the UK, offers an effective model of care for older patients with heart failure." ]

[ "19915206", "2641980", "19775439", "16569189", "12389880", "8090847", "7974314", "20122041", "18843564" ]

[ "Effects of a multifaceted minimal-lift environment for nursing staff: pilot results.", "How physical settings affect chronic mental patients.", "A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies.", "Use of an 'evidence-based implementation' strategy to implement evidence-based care of asthma into rural district hospital emergency departments.", "Effect of telephone follow-up on the physical well-being dimension of quality of life in patients with cancer.", "Effect of including a clinical example on the ability of physical therapists to apply information in a technical research report.", "Prospective controlled evaluation of the effect of a community based asthma education centre in a multiracial working class neighbourhood.", "Effects of a restraint minimization program on staff knowledge, attitudes, and practice: a cluster randomized trial.", "Physical health--a cluster randomized controlled lifestyle intervention among persons with a psychiatric disability and their staff." ]

[ "Nursing staff are at risk for musculoskeletal injuries because of the physical nature of patient handling. The purpose of this study is to examine the effectiveness of a multifaceted minimal-lift environment on reported equipment use, musculoskeletal injury rates, and workers' compensation costs for patient-handling injuries. The pilot study consists of a mixed measures design, with both descriptive and quasi-experimental design elements. The intervention consists of engineering (minimal-lift equipment), administrative (nursing policy), and behavioral (peer coach program) controls. The comparison nursing unit has received engineering controls only. The convenience sample includes nursing staff employed on two medical-surgical nursing units, who provide direct patient care at least 50% of the time. Nursing staff employed in a multifaceted lift environment report greater lift equipment use and experience less injury, with reduced worker's compensation costs.", "A study was conducted at New York State's Harlem Valley Psychiatric Center of the effects of physical changes in the ward environment on severely regressed psychotic inpatients and on the hospital staff who treat them. Two standard wards were remodeled according to principles in the scientific literature, preferences of those involved, and attempts to facilitate treatment goals. Within 8 months of the inauguration of the redesigned setting, there were selective behavior and attitude changes in both staff (N = 27) and patients (N = 37) as compared to four matched control wards (staff N = 44; patient N = 44): (1) staff mood level was raised significantly on a standard scale; (2) staff unscheduled absence rate was cut in half; (3) staff did not report significant improvement on scales of ward atmosphere and patient functioning; (4) patients themselves reported improvement in their self-images, but not in irritability, isolation, or depression; (5) patients reported significantly more satisfaction with the ward dayroom; (6) rate of patient violence decreased almost 50%.", "Significant resources and time are invested in the production of research knowledge. The primary objective of this randomized controlled trial was to evaluate the effectiveness of three knowledge translation and exchange strategies in the incorporation of research evidence into public health policies and programs.\n This trial was conducted with a national sample of public health departments in Canada from 2004 to 2006. The three interventions, implemented over one year in 2005, included access to an online registry of research evidence; tailored messaging; and a knowledge broker. The primary outcome assessed the extent to which research evidence was used in a recent program decision, and the secondary outcome measured the change in the sum of evidence-informed healthy body weight promotion policies or programs being delivered at health departments. Mixed-effects models were used to test the hypotheses.\n One hundred and eight of 141 (77%) health departments participated in this study. No significant effect of the intervention was observed for primary outcome (p < 0.45). However, for public health policies and programs (HPPs), a significant effect of the intervention was observed only for tailored, targeted messages (p < 0.01). The treatment effect was moderated by organizational research culture (e.g., value placed on research evidence in decision making).\n The results of this study suggest that under certain conditions tailored, targeted messages are more effective than knowledge brokering and access to an online registry of research evidence. Greater emphasis on the identification of organizational factors is needed in order to implement strategies that best meet the needs of individual organizations.\n The trial registration number and title are as follows: ISRCTN35240937 -- Is a knowledge broker more effective than other strategies in promoting evidence-based physical activity and healthy body weight programming?", "To determine if an evidence-based implementation (EBI) could lead to the successful implementation of evidence based care for adult asthma in small rural district hospitals.\n A controlled trial involving eight small rural hospitals (four each in the study and control groups) was conducted. Retrospective pre-intervention audits were conducted at all eight hospitals for 7 months (1 January 2004 to 31 July 2004) and evidence-practice gaps identified. An EBI was then used to implement established guidelines for the management of asthma in the study hospitals. Post-intervention audits were then performed over a period of 7 months (1 October 2004 to 31 April 2005).\n There were 52 presentations of asthma in the study hospitals in the pre-implementation phase and 47 post-implementation. The corresponding numbers for the control hospitals were 46 and 42 respectively. There were no statistically significant differences in the severity between the groups. Following the EBI there were significant improvements at the study hospitals for the documentation of severity (8% to 62%, p <0.001), use of spirometry (12% to 62%, p <0.001) and the use of written short-term asthma plans (9% to 26%, p = 0.05). There was a decrease in use of ipratropium in mild asthma (44% to 30%, p = 0.228), an increase in the use of systemic steroids (61% to 72%, p = 0.255) and no change in prescribing antibiotics for afebrile patients with asthma (21% to 21% p = 0.956). There was no significant change in practice at the control hospitals except for a decrease in the use of systemic steroids (48% to 21%, p = 0.011). For the six clinical indicators aggregate there was a significant increase in compliance with guidelines at the study hospitals (36% to 62%, p < 0.001) but no change at the control hospitals (31% to 31%, p = 0.970).\n The pre-intervention audits demonstrated low levels of compliance with asthma guidelines across six clinical indicators. An EBI significantly improved compliance across these six indicators, and no improvement was noted in the control hospitals. This study demonstrates that an EBI can alter clinical practice in small rural district hospitals.", "To evaluate the effect of telephone follow-up on the physical well-being dimension of health-related quality of life in patients with cancer.\n Randomized, controlled trial.\n Public teaching hospital.\n One hundred fifty patients with cancer who were discharged to home from the hospital.\n Patients received a telephone follow-up call 48-72 hours after discharge. Information was solicited regarding drug-related (and other) problems. Problems were addressed, and advice and support were given.\n Analysis of variance revealed no differences in the physical well-being dimension of health-related quality of life between patients who received telephone follow-up and a control group who did not. Sixty-eight percent of the follow-up group and 40% of the control group (p = 0.007) reported having had at least one contact with a health professional.\n One possible explanation for the lack of effect of the intervention is that high-risk patients in the control group received a similar intervention from other health care professionals. We suggest that telephone follow-up be coordinated among health professionals.", "The purpose of this study was to determine whether an example in a technical research report would affect application of content to hypothetical patient problems and to future patients.\n Subjects were 69 physical therapists who routinely used isokinetic equipment in the treatment of patients with knee joint pathologies.\n Thirty-five subjects (group 1) read a research report that described mathematical models for predicting preinjury quadriceps femoris and hamstring muscle performance. The report included an example of applying the information. The remaining 34 subjects (group 2) read the same research report with the example omitted. Subjects were asked to select appropriate prediction models and determine preinjury knee torques for two hypothetical patients. Subjects were also contacted 6 to 12 weeks after initial data collection to determine whether they had applied research report results in their treatments of patients.\n Chi-square analyses indicated manuscript type was not related to the selection of correct models, but group 1 subjects computed correct torque values more frequently than did group 2 subjects. Insufficient data were available regarding application of research report content to patients.\n The results indicate application of technically oriented research reports may be enhanced by including examples of applications. (Gross MT, Sekerak DK, Allen DD. Effect of including a clinical example on the ability of physical therapists to apply information in a technical research report.", "Previous work has indicated a high rate of non-attendance at hospital based clinics among young, multiracial asthmatic patients of lower socioeconomic class. The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated.\n A prospective controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were randomised to the usual follow up or the education centre plus usual follow up. Measurements were taken at entry into the study and again nine months later.\n At nine months patients randomised to the education centre had more preventive medications, more peak expiratory flow meters and better flow meter technique, more self-management plans, better knowledge of appropriate action to take when confronted with worsening asthma, less nocturnal awakening, and better self-reported asthma control than the control group. There was no difference between the study groups in measurements of compliance, hospital admission, days lost from school or work, or emergency room use.\n The main effects of education were on asthma knowledge and self-management skills, whilst improvements in asthma morbidity were small. Potential reasons for this include heterogeneous study population (in terms of baseline self-management skills, asthma severity, ethnicity and age), pragmatic study design, insensitivity of many of the measurements of morbidity, the modest effectiveness of a single time limited education programme, and inability to limit the effects of such a large community based study to the intervention group (there was a 67% reduction in asthma admissions during the study period from the geographical area targeted compared with a 22% reduction for the rest of Auckland).", "To evaluate the effects of a restraint minimization education program on staff knowledge and attitudes and use of physical restraints.\n Cluster-randomized controlled trial with nursing units as the basis for randomization.\n Forty group dwelling units for people with dementia.\n At baseline, there were 184 staff and 191 residents in the intervention group and 162 staff and 162 residents in the control group. At the 6-month follow-up, there were 156 staff and 185 residents (36 newly admitted) in the intervention group and 133 staff and 165 residents (26 newly admitted) in the control group.\n A 6-month education program for all nursing staff.\n Staff knowledge and attitudes and physical restraint use were measured before and after the education program.\n In the intervention group, staff knowledge about and attitudes toward restraint use changed, and the overall use of physical restraints decreased. A comparison including only residents present during the whole study period showed that the level of use was similar between the groups at baseline, whereas it was significantly lower in the intervention group at follow-up. Adjusted analyses showed that the odds of being restrained at follow-up were lower in the intervention group than in the control group. There was no significant change in the number of falls or use of psychoactive medication.\n The results indicate that staff education can increase knowledge, change attitudes, and reduce the use of physical restraints without any change in the incidence of falls or use of psychoactive drugs.", "The objective was to explore the impact on physical health of a lifestyle programme among persons with psychiatric disabilities, and their caregivers. Their satisfaction with the intervention was also assessed. Somatic comorbidity and an increased mortality related to the lifestyle among persons with psychiatric disabilities are well known. Few randomized controlled trials have been aimed specifically at lifestyle issues among persons with a psychiatric disability. This trial includes clients with psychiatric disabilities living in supported housing and their staff. Forty-one persons with a DSM-?V diagnosis of severe mental illness from psychiatric disability from 10 supported housing facilities and 41 of their caregivers participated in this 12-month study during 2005-2006 in Sweden. The supported housing facilities with residents and staff were randomly assigned to either a health intervention programme or a control programme with an aesthetic content. The presence of metabolic syndrome and changes in the mean of physiological parameters such as Hba1c, P-glucose, P-insulin, lipids, blood pressure, physical working capacity, body mass index, Heart Score were investigated and participants' satisfaction assessed. There was a significant reduction in the mean of metabolic syndrome criteria in the intervention group compared with the control group at the follow-up. The participants expressed satisfaction with the programme. The results indicate that health interventions on lifestyle issues when involving carers are appreciated, feasible and could be successful in reducing some health-related risk factors among persons with psychiatric disabilities." ]

[ "19135415", "8589019", "8082100", "9391542", "10595816", "15202162", "8265095", "10388135", "8695248" ]

[ "Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial.", "Ondansetron versus granisetron, both combined with dexamethasone, in the prevention of cisplatin-induced emesis. Italian Group of Antiemetic Research.", "Ondansetron versus granisetron in the prevention of chemotherapy-induced nausea and vomiting. Results of a prospective randomized trial.", "A comparative study of intravenous granisetron versus intravenous and oral ondansetron in the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy.", "A prospective randomized trial of the anti-emetic efficacy of ondansetron and granisetron during bone marrow transplantation.", "Single-dose oral granisetron versus multidose intravenous ondansetron for moderately emetogenic cyclophosphamide-based chemotherapy in pediatric outpatients with acute lymphoblastic leukemia.", "Ondansetron compared with granisetron in the prophylaxis of cisplatin-induced acute emesis: a multicentre double-blind, randomised, parallel-group study. The Ondansetron and Granisetron Emesis Study Group.", "A Comparison of Oral Ondansetron and Intravenous Granisetron for the Prevention of Nausea and Emesis Associated with Cisplatin-Based Chemotherapy.", "An open randomised cross-over study on granisetron versus ondansetron in the prevention of acute emesis induced by moderate dose cisplatin-containing regimens." ]

[ "Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT(3))-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy. In this phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group, active-comparator trial, we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting, both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy.\n Between July 5, 2006, and May 31, 2007, 1143 patients with cancer who were receiving highly emetogenic chemotherapy (ie, cisplatin, or an anthracycline and cyclophosphamide combination [AC/EC]) were recruited from 75 institutions in Japan, and randomly assigned to either single-dose palonosetron (0.75 mg), or granisetron (40 microg/kg) 30 min before chemotherapy on day 1, both with dexamethasone (16 mg intravenously) on day 1 followed by additional doses (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC) on days 2 and 3. A non-deterministic minimisation method with a stochastic-biased coin was applied to the randomisation of patients. Covariates known to effect emetic risk, such as sex, age, and type of highly emetogenic chemotherapy, were used as stratification factors of minimisation to ensure balance between the treatment groups. Primary endpoints were the proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) during the acute phase (0-24 h postchemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with a complete response during the delayed phase (24-120 h postchemotherapy; superiority comparison with granisetron). The non-inferiority margin was predefined in the study protocol as a 10% difference between groups in the proportion of patients with complete response. The palonosetron dose of 0.75 mg was chosen on the basis of two dose-determining trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses (modified intention to treat). This trial is registered with ClinicalTrials.gov, number NCT00359567.\n 1114 patients were included in the efficacy analyses: 555 patients in the palonosetron group and 559 patients in the granisetron group. 418 of 555 patients (75.3%) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients (73.3%) in the granisetron group (mean difference 2.9% [95% CI -2.70 to 7.27]). During the delayed phase, 315 of 555 patients (56.8%) had complete response in the palonosetron group compared with 249 of 559 patients (44.5%) in the granisetron group (p<0.0001). The main treatment-related adverse events were constipation (97 of 557 patients [17.4%] in the palonosetron group vs 88 of 562 [15.7%] in the granisetron group) and raised concentrations of serum aminotransferases (aspartate aminotransferase: 24 of 557 [4.3%] vs 34 of 562 [6.0%]; alanine aminotransferase: 16 of 557 [2.9%] vs 33 of 562 [5.9%]); no grade 4 main treatment-related adverse events were reported.\n When administered with dexamethasone before highly emetogenic chemotherapy, palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase, with a comparable safety profile for the two treatments.\n Taiho Pharmaceutical (Tokyo, Japan).", "Differences in pharmacodynamic and pharmacokinetic characteristics among serotonin-receptor antagonists have been reported in preclinical studies. This prompted us to carry out a study to determine whether such differences are important in terms of clinical efficacy or tolerability.\n 973 consecutive cancer patients scheduled to receive cisplatin for the first time (at doses > or = 50 mg2), entered a double-blind multicenter randomized study comparing intravenous ondansetron 8 mg versus granisetron 3 mg. Dexamethasone 20 mg was added to both serotonin antagonists. On days 2 to 4 after chemotherapy all patients received oral metoclopramide plus intramuscular dexamethasone as antiemetic prophylaxis for delayed emesis. Nausea and vomiting were assessed daily until day 6 after chemotherapy.\n We evaluated 966 patients (483 receiving ondansetron and 483 granisetron). Complete protection from acute vomiting/nausea was obtained in 79.3%/72.0% of patients receiving ondansetron and in 79.9%/71.8% of those receiving granisetron. Complete protection from delayed vomiting/nausea as obtained in 69.7%/52.9% and 70.0%/49.6% of patients receiving the ondansetron or granisetron regimens, respectively. Adverse effects were mild and not significantly different between the two antiemetic regimens.\n Ondansetron 8mg and granisetron 3 mg, both combined with dexamethasone, showed similar efficacy and tolerability in the prevention of cisplatin-induced emesis. The choice between the two regimens can be dictated by their respective purchase prices.", "A single-institution, prospective, randomized open trial was performed to compare ondansetron and granisetron in the prevention of chemotherapy-related nausea and vomiting. The effect of antemetic drugs was analyzed indipendently for patients treated with highly emetogenic chemotherapy (Study 1), and those treated with moderately emetogenic regimens (Study 2).\n In Study 1, 182 patients treated with chemotherapeutic regimens containing high dose cisplatin (more than 70 mg/m2) were randomized to receive 24 mg of ondasentron intravenously (i.v.) or 3 mg of granisetron i.v. for the control of acute emesis. Patients treated with fractionated chemotherapy and those followed-up for delayed emesis also received 8 mg of ondansetron orally twice a day or 3 mg of granisetron i.v. on the days after Day 1. In Study 2, 164 patients were randomized to receive either 16 mg of ondansetron i.v. or 3 mg of granisetron i.v. to prevent emesis in the first 24 hours.\n In the ondansetron group in Study 1, a complete response (CR) (i.e., no vomiting, nausea possible) from acute emesis was achieved in 52% of cases, a major response (MR) in 29%, and a minor response (MiR) in 14%. In the granisetron group in Study 1, a CR was seen in 49% of patients, an MR in 24%, and an MiR in 12%. Failure was recorded in 5% and 15% of cases in the ondansetron and granisetron groups, respectively. No statistically significant difference in any response category was seen between the two groups. In the ondansetron group, a complete protection from delayed emesis was recorded in 39% of cases, an MR in 32%, an MiR in 21%, and failure in 16%. In the granisetron arm, 36% of the patients had a CR, 22% had an MR, 14% had an MiR, and 14% experienced treatment failure. Again, these differences did not reach statistical significance. In Study 2, no statistical significant difference was observed between the ondansetron arm and the granisetron arm, both for acute and delayed emesis. Both ondansetron and granisetron were tolerated very well by most patients, with no severe side effects. In the group of patients treated with ondansetron, however, the incidence of headache (9%) was higher than in the group treated with granisetron (4%).\n These data suggest that although both ondansetron and granisetron are very effective drugs for the control of acute emesis, their efficacy against delayed emesis is still not entirely satisfactory.", "We conducted a prospective, randomized, open, single-center, parallel group study comparing the anti-emetic efficacy and toxicity of granisetron with that of ondansetron in patients receiving moderately emetogenic chemotherapy. From December 1994 to May 1995, patients who were to receive moderately emetogenic chemotherapy for the first time or who had not received chemotherapy (80 to 100 mg/m2 of cisplatin or 40 mg/m2 of doxorubicin) within 4 weeks previously were enrolled in this study. The following anti-emetic regimens were used: 3 mg of granisetron were given intravenously before chemotherapy for a single dose; 8 mg of ondansetron were given intravenously before chemotherapy and then every 8 hours for a total of 3 doses, plus 8 mg of an oral maintenance dose every 12 hours for 5 consecutive days. We evaluated 97 patients (48 received granisetron and 49 received ondansetron). In the first 24 hours after chemotherapy, complete and major responses were achieved in 76.6% of the patients receiving granisetron and in 72.9% of patients receiving ondansetron (p = 0.9033). Additionally, there was no difference in the control of delayed nausea and vomiting between the two groups (51.1% versus 54.2%, p = 0.9200), and there were no significant adverse effects or toxicities. We have concluded that a single dose of granisetron is as effective in prophylaxis of emesis induced by moderately emetogenic chemotherapy as a triple dose of ondansetron plus oral maintenance.", "To determine the comparative anti-emetic efficacy of ondansetron and granisetron in patients undergoing bone marrow transplantation, we performed a double-blind, randomized trial in pediatric and adult patients receiving transplants at the University of Minnesota. The results in 187 patients stratified by age (<18 years, n = 51; > or =18 years, n = 136) were analyzed. The average number of emetic episodes in the entire group from day -7 to 2 was 0.86/day for patients receiving ondansetron and 0.73/day for those receiving granisetron (p = 0.32). No differences were noted between the two drugs in total days of complete or major control of emesis or in the number of requests for additional drugs to alleviate symptoms of nausea. The use of total-body irradiation-containing conditioning regimens was associated with a decreased number of emetic episodes compared with regimens of chemotherapy alone. Perceived nausea was evaluated using a nausea scoring system, and no differences were apparent between the granisetron and ondansetron groups; however, reported nausea was significantly higher in females (p<0.01) and in the adult population (p = 0.05). We conclude that both ondansetron and granisetron provide good control of nausea and vomiting experienced with conditioning regimens for bone marrow transplantation. The relative cost of the drugs within an institution must be considered in developing standard anti-emetic regimens for bone marrow transplantation.", "This prospective study was designed to compare the efficacy of ondansetron with granisetron in terms of complete emesis control and time spent in an ambulatory care setting in children with acute lymphoblastic leukemia (ALL) undergoing moderately emetogenic cyclophosphamide-based chemotherapy. The costs for both treatments are also examined. A total of 33 children (mean age: 7.8 +/- 4.9 year) were studied during 66 chemotherapy cycles. Analysis was based on 33 courses of a single oral dose of granisetron and 33 courses of ondansetron incorporating 2 intravenous doses of ondansetron 0.15 mg/kg followed by 1 dose of the same dosage orally. There was no significant difference between the 2 treatments in terms of overall efficacy (McNemar's chi-square test). Twenty of 33 patients (60.6%) receiving granisetron and 15 of 33 patients (45.5%) receiving ondansetron experienced no emesis 24 h after chemotherapy (p = .227). Boys experienced greater rates of vomiting than did girls despite antiemetic treatment; however, no apparent reason for the gender discrepancy was noted. Both antiemetic regimens have similar antiemetic efficacy for treating the moderately emetogenic effects associated with cyclophosphamide-based chemotherapy. It is possible that the granisetron regimen may be preferable because it is simpler to administer and more cost-effective.", "This is the first international, multi-centre, double-blind, randomised, parallel group study to directly compare the efficacy and safety profile of a single intravenous dose of ondansetron (8 or 32 mg) with granisetron (3 mg) in the control of cisplatin-induced acute emesis. A total of 496 patients were randomised to receive one of three anti-emetic treatments prior to cisplatin chemotherapy (> or = 50 mg/m2). Of these, 165 and 162 patients received 8 and 32 mg of ondansetron, respectively, and 169 patients received 3 mg of granisetron. Complete control of emesis (0 emetic episodes) over 24 h was reported in 59% of patients in the 8-mg ondansetron group, 51% of patients in the 32-mg ondansetron group and 56% of patients in the granisetron group. Complete or major control (< or = 2 emetic episodes) was achieved in 76 and 74% of patients in the 8- and 32-mg ondansetron group, respectively, compared with 78% of patients in the granisetron group. Nausea graded none or mild 24 h after the start of cisplatin infusion was reported in 71 and 69% of patients in the 8- and 32-mg ondansetron groups, respectively, and in 73% of patients in the granisetron group. There were no significant differences between the treatment groups when global satisfaction scores were compared. Logistic regression models were fitted to assess any interaction between treatments and prognostic factors (age, gender, alcohol use, cisplatin dose or concomitant chemotherapy) on complete or major response, but there was no evidence of interaction for any factor. All three anti-emetic treatments were well tolerated and no severe or unexpected drug-related adverse events were observed with ondansetron or granisetron. Headache, the most reported drug-related adverse event for all three treatment groups, occurred in 9% of all patients. In summary, no significant difference was observed between any of the treatment groups with respect to emesis, nausea or drug-related adverse events.", "PURPOSE: To compare the efficacy and safety of oral ondansetron with i.v. granisetron each given as a single dose prior to administration of highly emetogenic cisplatin chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed malignancies were randomized to receive a single 24 mg ondansetron hydrochloride tablet plus a 50 ml i.v. infusion of normal saline, or a single 10 µg/kg (50 ml) i.v. infusion of granisetron plus a placebo tablet in this multicenter, double-blind, parallel-group trial. Study drug was administered 30 min prior to a single i.v. infusion of cisplatin (50-75 mg/m&sup2;), given over a period of </= 3 h. Concurrent administration of corticosteroids was not allowed. Efficacy measurements included the number of emetic episodes, need for rescue medication, and patient assessments of nausea and appetite. Complete response (CR) was defined as no emetic episodes, rescue, or withdrawal; major response was defined as one or two episodes. Safety was evaluated by monitoring adverse events and changes in laboratory parameters. RESULTS: A total of 371 patients entered the study and received study drug, of whom 184 received ondansetron and 187 received granisetron. For all parameters tested, a single 24 mg oral ondansetron tablet was at least as effective as i.v. granisetron. CR was achieved in 58% of ondansetron-treated patients and 51% of granisetron-treated patients (95% confidence interval on the difference: -4% to 17%). Subjective assessments revealed no difference with regard to complete control of nausea, appetite, or satisfaction with antiemetic therapy. Both drugs were well tolerated; the most common adverse event was headache. CONCLUSION: A single 24 mg oral dose of ondansetron is at least as safe and effective as a single i.v. infusion of 10 µg/kg of granisetron in preventing nausea and vomiting induced by highly emetogenic cisplatin chemotherapy.", "The aim of the study was to compare granisetron (GRA) with ondansetron (OND) in the prevention of acute emesis in consecutive chemotherapy-naive patients admitted to our department to receive a cytotoxic treatment containing cisplatinum (CP) at a dose > or = 50 mg/m2. Eligible patients were randomised at their first cycle to receive either OND or GRA with cross-over of the anti-emetic treatment on the second cycle. The cytotoxic treatments included five different multidrug regimens containing CP (median dose 60 mg/m2, range 50-70 mg/m2) administered on day 1 and repeated every 21-28 days. OND was administered at the dose of 8 mg x 3 i.v. on day 1 and 8 mg x 2 orally on day 2. GRA was always administered at the dose of 3 mg i.v. on day 1. 124 patients entered the study. 58 patients received OND at their first cycle and 66 received GRA. Complete protection of acute emesis with OND and GRA was observed, with the first and second cycles combined as follows: nausea 53 and 60%, vomiting 68 and 71%, respectively (no statistically significant difference). The cross-over analysis comprising 101 patients confirmed no difference between the two anti-emetic treatments. 21 patients (19%) on OND and 14 patients (12%) on GRA suffered headaches (P = 0.15). 25 (25%) patients preferred OND, 45 (45%) preferred GRA, while 31 (30%) expressed no preference (P = 0.003). However, these differences also depended on the sequence of anti-emetics in the cross-over. In conclusion, in this study, a single dose of GRA is demonstrated to be as effective as multiple doses of OND in the prevention of acute emesis." ]

[ "20145608", "17690340", "17803667", "18410562", "18813028", "18701826", "12150178", "12150179", "22472744" ]

[ "Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients.", "Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations.", "Efficacy of Lactobacillus rhamnosus GG in acute watery diarrhoea of Indian children: a randomised controlled trial.", "Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children.", "Efficacy of high-dose Lactobacillus rhamnosus GG in controlling acute watery diarrhea in Indian children: a randomized controlled trial.", "Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A, and Lactobacillus plantarum PL02 in the prevention of antibiotic-associated diarrhea in children: a randomized controlled pilot trial.", "Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea.", "Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers.", "Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial." ]

[ "Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.\n In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days.\n Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1.\n The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).", "To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children. Design Randomised controlled clinical trial in collaboration with family paediatricians over 12 months.\n Primary care.\n Children aged 3-36 months visiting a family paediatrician for acute diarrhoea.\n Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68.\n Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded.\n 571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P<0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P<0.001) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups.\n Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data.\n Current Controlled Trials ISRCTN56067537 [controlled-trials.com].", "To evaluate the role of Lactobacillus rhamnosus GG (LGG) as probiotic in acute watery diarrhoea (AWD).\n Hospital-based study.\n Randomised, controlled, blinded trial.\n All patients of AWD (n = 684) admitted over 1-year period were invited to participate in the study as per predefined inclusion and exclusion criteria and were randomised to intervention and control groups. After adequate rehydration the intervention group (n = 330) received ORS with probiotic powder containing 60 million cells of LGG, while the control group (n = 332) received ORS alone twice daily for a minimum period of 7 days or till diarrhoea ceased. During the study period all patients received ORS and/or IV fluids for ongoing losses, and nutritional supplementation. None of them received any antibiotic or antidiarrhoeal medication. After exclusion of 16 patients, 646 (323 in each arm) patients completed the study. The daily frequency and total duration of diarrhoea and vomiting and the length of hospital stay were studied. Data were analysed by SPSS-10 software. Statistical significance was calculated by Student's t-test and chi2-test.\n Rotavirus was isolated in 75.85%. There was no significant difference between treatment groups in the daily frequency or duration of diarrhoea or vomiting or in the length of hospital stay. No complication was observed from the use of LGG.\n LGG supplementation does not decrease the frequency and duration of diarrhoea and vomiting in children with AWD, and does not reduce hospital stay in these patients.", "Convincing evidence that probiotic administration can lower the risk of antibiotic-associated diarrhoea is limited to certain micro-organisms.\n To determine the efficacy of administration of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) for the prevention of antibiotic-associated diarrhoea in children.\n Children (aged 3 months to 14 years) with common infections were enrolled in a double-blind, randomized, placebo-controlled trial in which they received standard antibiotic treatment plus 2 x 10(10) colony forming units of a probiotic (n = 120) or a placebo (n = 120), administered orally twice daily throughout antibiotic treatment. Analyses were by intention to treat.\n Any diarrhoea (>or=3 loose or watery stools/day for >or=48 h occurring during or up to 2 weeks after the antibiotic therapy) occurred in nine (7.5%) patients in the probiotic group and in 20 (17%) patients in the placebo group (relative risk, RR 0.45, 95% confidence interval, CI 0.2-0.9). Three (2.5%) children in the probiotic group developed AAD (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared to nine (7.5%) in the placebo group (RR 0.33, 95% CI 0.1-1.06). No adverse events were observed.\n Administration of L. rhamnosus (strains E/N, Oxy and Pen) to children receiving antibiotics reduced the risk of any diarrhoea, as defined in this study.", "To evaluate the effective dose of Lactobacillus rhamnosus GG (LGG) as probiotic in acute watery diarrhea (AWD) in Indian children.\n Hospital-based study.\n Randomized, controlled, blinded trial.\n All patients of AWD admitted over 1 year were included in the study. They were randomized into 3 groups to receive either only oral rehydration solution (ORS) (group A/control), ORS+LGG powder containing 10(10) colony forming units (CFU) (group B), or ORS+LGG powder containing 10(12) CFU (group C) twice daily for a minimum period of 7 days or until diarrhea stopped along with correction of dehydration. None of them received any other drug such as antibiotic or antidiarrheal medication. The duration and frequency of diarrhea and vomiting were studied. Data were analyzed by SPSS-10 software.\n The study comprised of 559 patients, group A/controls (n=185), group B (n=188), and group C (n=186). All the groups were similar with respect to age, number of breastfed infants, presentation with dehydration, degree of protein energy malnutrition, and rotavirus infection. The frequency and duration of diarrhea, requirement for intravenous therapy, and hospital stay were significantly lower in both the intervention groups compared with the controls. There was no significant difference between the 2 intervention groups. No complication was observed from the doses of LGG used.\n Both the doses of LGG (10(10) and 10(12) CFU) were equally effective to decrease the frequency and duration of diarrhea and reduction in hospital stay in patients of AWD.", "To determine the efficacy of a combination of Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A and Lactobacillus plantarum PL02 for the prevention of antibiotic-associated diarrhea in children.\n Seventy-eight children (age: 5 months to 16 years) with otitis media, and/or respiratory tract infections, and/or urinary tract infections were enrolled in a double-blind randomized control trial in which they received standard antibiotic treatment plus a food supplement containing 10(8) colony-forming units of B. longum, L. rhamnosus and L. plantarum (n = 40) or a placebo (n = 38) orally twice daily for the duration of antibiotic treatment.\n Patients receiving probiotics had a similar rate of diarrhea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) as those receiving placebo (relative risk 0.5, 95% CI 0.06-3.5). The mean number of stools per day was significantly lower in the experimental group (mean difference -0.3 stool/day, 95% CI -0.5 to -0.07). No adverse events were reported.\n The administration of the 3 probiotics did not significantly alter the rate of diarrhea, although it reduced the frequency of stools per day. As the overall frequency of diarrhea was surprisingly low, these results should be interpreted with caution.\n 2008 S. Karger AG, Basel.", "Oral bacteriotherapy promotes recovery from acute childhood diarrhea, but few strains have been shown to have therapeutic potentials. We examined the effect of two newly identified probiotic Lactobacillus strains in acute childhood diarrhea.\n Sixty-nine children were randomized during hospitalization for acute diarrhea to receive a mixture of Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 10(10) colony-forming units of each strain or placebo twice daily for 5 days. Before selection of these stains their potential probiotic characteristics were demonstrated in vitro and in healthy volunteers.\n In patients receiving probiotics, the diarrheal phase was reduced by 20%. The duration of diarrhea was 82 h in the treatment group vs. 101 h in the control group (not significant, P = 0.07). However, 3 of 30 patients from the treatment group vs. 13 of 39 from the control group still had loose stools at the end of the study period (P = 0.03). In patients with diarrhea for <60 h before start of treatment (early intervention), a clear effect of the probiotics was demonstrated (80 h in the treatment group vs. 130 h in the control group, P = 0.003). After early intervention, the length of hospitalization was reduced by 48% (3.5 vs. 1.7 days, P = 0.03). At the end of the intervention, rotavirus antigen was found in 12% of patients from the treatment group vs. 46% from the control group (P = 0.02).\n The two probiotics, L. rhamnosus 19070-2 and L. reuteri DSM 12246, ameliorated acute diarrhea in hospitalized children and reduced the period of rotavirus excretion. Oral bacteriotherapy was associated with a reduced length of hospital stay. The beneficial effects were most prominent in children treated early in the diarrheal phase.", "Certain strains of lactobacilli have been shown to promote recovery from rotavirus enteritis in hospitalized children. Few studies have examined the effect of probiotics in nonhospitalized children with mild diarrhea.\n We studied in a randomized placebo-controlled trial the effect of lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 10(10) colony-forming units of each strain twice daily for 5 days, on acute diarrhea in children in a cohort of children recruited from local day-care centers. The duration of diarrhea and assessment of stool consistency were recorded by the parents.\n In patients treated with the selected Lactobacillus strains, the mean duration of diarrhea after intervention was reduced (76 h in patients treated with probiotics vs. 116 h in the placebo group; P = 0.05). In patients with diarrhea for <60 h before start of treatment (early intervention), a more pronounced effect of probiotics was found. The time to recovery after early treatment was 79 h vs. 139 h in the placebo group (P = 0.02); 1 of 17 patients treated early vs. 6 of 13 in the control group still had loose stools 120 h after start of treatment (P = 0.03).\n In children from day-care centers with mild gastroenteritis, the combination of L. rhamnosus 19070-2 and L. reuteri DSM 12246 was effective in reducing the duration of diarrhea.", "Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients.\n A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment.\n Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60).\n In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD." ]

[ "15632336", "16202939", "12850599", "15050984", "15333602", "18307077", "17077230", "16022849", "20399951" ]

[ "Direct access to emergency contraception through pharmacies and effect on unintended pregnancy and STIs: a randomized controlled trial.", "Advance supply of emergency contraception: a randomized trial in adolescent mothers.", "Advance supply of emergency contraception. effect on use and usual contraception--a randomized trial.", "The effects of advance provision of emergency contraception on adolescent women's sexual and contraceptive behaviors.", "Effect of advanced provision of emergency contraception on women's contraceptive behaviour: a randomized controlled trial.", "Advance provision of emergency contraceptive pills reduces treatment delay: a randomised controlled trial among Swedish teenage girls.", "Impact of increased access to emergency contraceptive pills: a randomized controlled trial.", "Advanced provision of emergency contraception to postnatal women in China makes no difference in abortion rates: a randomized controlled trial.", "A randomized controlled trial of the effect of advanced supply of emergency contraception in postpartum teens: a feasibility study." ]

[ "It is estimated that half of unintended pregnancies could be averted if emergency contraception (EC) were easily accessible and used.\n To evaluate the effect of direct access to EC through pharmacies and advance provision on reproductive health outcomes.\n A randomized, single-blind, controlled trial (July 2001-June 2003) of 2117 women, ages 15 to 24 years, attending 4 California clinics providing family planning services, who were not desiring pregnancy, using long-term hormonal contraception or requesting EC.\n Participants were assigned to 1 of the following groups: (1) pharmacy access to EC; (2) advance provision of 3 packs of levonorgestrel EC; or (3) clinic access (control).\n Primary outcomes were use of EC, pregnancies, and sexually transmitted infections (STIs) assessed at 6 months; secondary outcomes were changes in contraceptive and condom use and sexual behavior.\n Women in the pharmacy access group were no more likely to use EC (24.2%) than controls (21.0%) (P = .25). Women in the advance provision group (37.4%) were almost twice as likely to use EC than controls (21.0%) (P<.001) even though the frequency of unprotected intercourse was similar (39.8% vs 41.0%, respectively, P = .46). Only half (46.7%) of study participants who had unprotected intercourse used EC over the study period. Eight percent of participants became pregnant and 12% acquired an STI; compared with controls, women in the pharmacy access and advance provision groups did not experience a significant reduction in pregnancy rate (pharmacy access group: adjusted odds ratio [OR], 0.98; 95% confidence interval [CI], 0.58-1.64; P = .93; advance provision group: OR, 1.10; 95% CI, 0.66-1.84, P = .71) or increase in STIs (pharmacy access group: adjusted OR, 1.08, 95% CI, 0.71-1.63, P = .73; advance provision group: OR, 0.94, 95% CI, 0.62-1.44, P = .79). There were no differences in patterns of contraceptive or condom use or sexual behaviors by study group.\n While removing the requirement to go through pharmacists or clinics to obtain EC increases use, the public health impact may be negligible because of high rates of unprotected intercourse and relative underutilization of the method. Given that there is clear evidence that neither pharmacy access nor advance provision compromises contraceptive or sexual behavior, it seems unreasonable to restrict access to EC to clinics.", "To examine whether the advanced provision of emergency contraception (AEC) to parenting youth would increase emergency contraception (EC) utilization, and whether AEC would impact the rates of unprotected sex and contraception use.\n Subjects were randomized to receive either information about EC or information and an actual supply of AEC. Subjects were interviewed at baseline, 6 and 12-month follow-up.\n Urban non-medical case management office.\n 160 adolescent mothers (ages 13 to 20) who were receiving case management services.\n Advance supply of emergency contraception.\n Emergency contraception use, sexual activity, unprotected intercourse, contraceptive methods and use.\n Parenting teens who received AEC were much more likely to have used it than the control group at the 6-month interview (83% vs. 11%) and the 12-month interview (64% vs. 17%). Teens in the AEC treatment group were more likely to have unprotected sex at the 12-month follow-up interview (69% vs. 45%). There was no difference in condom use between the groups at either the 6-month, or the 12-month follow-up interviews.\n Advance provision of emergency contraception in parenting teens increases the likelihood of its use, and does not affect the use of condoms, or hormonal methods of birth control. Parenting teens who receive AEC may be more likely to have unprotected sex.", "To evaluate whether advance provision of emergency contraception increases its use and/or adversely affects usual contraceptive practices.\n We performed a randomized controlled trial comparing advance provision of emergency contraception with usual care in 370 postpartum women from an inner-city public hospital. Participants were followed for 1 year; 85% were available for at least one follow-up session. All participants received routine contraceptive education. The intervention group received a supply of emergency contraception (eight oral contraceptive pills containing 0.15 mg of levonorgestrel and 30 microg of ethinyl estradiol) and a 5-minute educational session. We compared use of emergency contraception and changes in contraceptive behaviors between groups.\n Women provided with pills were four times as likely to have used emergency contraception as women in the control group over the course of the year (17% versus 4%; relative risk [RR] 4.0; 95% confidence interval [CI] 1.8, 9.0). Women were no more likely to have changed to a less effective method of birth control (30% versus 33%; RR 0.92; 95% CI 0.63, 1.3), or to be using contraception less consistently (18% versus 25%; RR 0.74; 95% CI 0.45, 1.2). About half of each group reported at least one episode of unprotected intercourse during follow-up, but women who received emergency contraception were six times as likely to have used it (25% versus 4%; RR 5.8; 95% CI 2.1, 16.4).\n Advance provision of emergency contraception significantly increased use without adversely affecting use of routine contraception. It is safe and appropriate to provide emergency contraception to all postpartum women before discharge from the hospital.", "Advance provision of emergency contraception (EC) may increase timely access and improve effectiveness, but the impact on adolescent sexual and contraceptive behaviors is not known.\n To determine whether adolescents given advance EC have higher sexual and contraceptive risk-taking behaviors compared to those obtaining it on an as-needed basis.\n Randomized trial conducted at urban, hospital-based adolescent clinic in Pittsburgh, PA, from June 1997 to June 2002.\n 301 predominantly minority, low-income, sexually active adolescent women, age 15-20 years, not using long-acting contraception.\n Advance EC vs instruction on how to get emergency contraception.\n Self-reported unprotected intercourse and use of condoms, EC, and hormonal contraception ascertained by monthly 10-minute telephone interviews for 6 months post-enrollment. Reported timing of EC use after unprotected intercourse.\n At both 1- and 6-month followup interviews, there were no differences between advance EC and control groups in reported unprotected intercourse within the past month or at last intercourse. At 6 months, more advance EC participants reported condom use in the past month compared to control group participants (77% vs 62%, P=0.02), but not at last intercourse (advance EC 83% vs control 78%, P=0.34). There were no significant differences by group in hormonal contraception use reported by advance EC or control groups in the past month (44% vs 53%, P=0.19) or at last intercourse (48% vs 58%, P=0.20). At the first followup, the advance group reported nearly twice as much EC use as the control group (15% vs 8%, P=0.05) but not at the final followup (8% vs 6%, P=0.54). Advance EC group participants began their EC significantly sooner (11.4 hours vs 21.8 hours, P=0.005).\n Providing advance EC to adolescents is not associated with more unprotected intercourse or less condom or hormonal contraception use. In the first month after enrollment, adolescents provided with advance EC were nearly twice as likely to use it and began EC sooner, when it is known to be more effective.", "Emergency contraception (EC) can prevent pregnancy but is under-used. Advanced provision increases use but the effect on contraceptive behaviour varies.\n Women aged 18-45 years, using less effective contraceptives, were randomized to either advanced provision of three courses of EC (intervention) or to obtaining each course from clinic (control). EC use and contraceptive behaviour were monitored for 1 year.\n In all, 1030 women were recruited in 6 months. The mean+/-SD number of courses of EC used in intervention versus control group was 0.56+/-1.2 versus 0.20+/-0.6 (P<0.001). In the intervention group, 47% women aged <26 years used at least one course of EC compared with 23% of older women (P<0.001). The majority of women used condoms before (intervention 89%, control 91%) and during the study (89% for both groups). Consistency of contraceptive use was higher during the study (65 versus 60% of women in both groups) (P<0.001). There were 17 unplanned pregnancies, eight in the intervention group, six of whom did not use EC in the conception cycle.\n Advanced provision increases EC use especially among young women in Hong Kong. Contraceptive choice and consistency of use remains the same even among young women.", "To evaluate an intervention involving advance provision of emergency contraceptive pills (ECP) to Swedish teenage girls.\n Some 420 girls aged 15-19, requesting ECP at a local youth clinic were randomly assigned to intervention group (IG) (n=214) or control group (CG) (n=206). Both groups received ECP on request. The IG received one extra dose of ECP, condoms and an information leaflet regarding ECP and condom use. Main outcome measures were differences between IG and CG regarding ECP use, time span between unprotected intercourse and ECP intake, contraceptive use, and sexual risk taking. Questionnaires were completed at the initial visit, and the girls were followed up by structured telephone interviews 3 and 6 months later.\n At the 3-month follow-up, girls in the IG were almost twice as likely to have used ECP compared to girls in the CG (IG: 24.0%, CG: 13%, p=0.02), and they used it sooner after unprotected intercourse (mean time IG: 13.61 h, CG: 25.47 h, p=0.007). Significant differences persisted 6 months after the intervention (ECP use IG: 31%, CG: 19%, p=0.01; and mean time IG: 15.59 h, CG: 26.38 h, p=0.006). No significant differences were found in the use of regular hormonal contraceptives or condoms at either follow-up. About 40% of the girls in both groups had risked pregnancy during the follow-up period, but only half of these had used ECP.\n This intervention shortened the time interval from unprotected intercourse to pill intake without jeopardising contraceptive use and without increasing sexual risk taking.", "To assess how a strategy to maximize access to emergency contraceptive pills would affect rates of pregnancy and sexually transmitted infections.\n Sexually active women, 14-24 years old, were randomly assigned to two methods of access to emergency contraceptive pills: increased access (two packages of pills dispensed in advance with unlimited resupply at no charge) or standard access (pills dispensed when needed at usual charges). Participants were followed for 1 year to assess incidence of pregnancy, gonorrhea, chlamydia, and trichomonas.\n The numbers of women enrolled in the increased and standard access groups were 746 and 744, respectively. More than 93% of participants completed a full year of follow-up. The incidence of pregnancy was similar in both groups (increased access group: 9.9/100 woman years, 95% confidence interval [CI] 7.7-12.6; standard access group: 10.5/100 woman years, 95% CI 8.2-13.2). Aggregate rates of gonorrhea, chlamydia, and trichomonas were also similar in the two groups (increased access group: 6.9/100 woman years, 95% CI 5.1-9.1; standard access group: 7.6/100 woman years, 95% CI 5.7-9.9). The increased access group used emergency contraceptive pills substantially more often and sooner after coitus than the standard access group. No other differences were noted between groups in self-reported measures of sexual behavior and contraceptive use.\n This intensive strategy to enhance access to emergency contraceptive pills substantially increased use of the method and had no adverse impact on risk of sexually transmitted infections. However, it did not show benefit in decreasing pregnancy rates.\n II-1.", "Emergency contraception (EC) prevents pregnancy, and it has been suggested that widespread use could reduce abortion rates; however, the use is limited. Providing EC in advance of need increases use, but there is no direct evidence that it reduces unintended pregnancy. In a randomized controlled trial of 2000 women after childbirth in Shanghai, all women not wishing to use hormonal contraception or an intrauterine device (IUD) were given a supply of condoms. Those in the intervention group also received three courses of mifepristone 10 mg with instructions for use as EC. Follow-up was by telephone at 16, 32 and 52 weeks. Over 88% of women in both groups completed 1 year of follow-up. Women with a supply of EC were more than twice as likely to use it, and to use it more than once (p<.001 for both) than women without a supply. There was no difference in pregnancy rates at 1 year (38/832 vs. 32/817). EC was not used in 89% of conception cycles, as women did not recognize the need for it. Increased use of EC may not reduce abortion rates.", "The study was conducted to test the feasibility of conducting a randomized controlled contraceptive trial in postpartum teens and to assess whether postpartum advanced supply of emergency contraception (EC) to teenaged mothers helps to prevent repeat pregnancies of close proximity.\n We performed a randomized controlled trial of 50 postpartum teens at an urban academic medical center. Participants in the intervention arm received routine postpartum contraceptive care and advanced supply of one pack of EC pills with unlimited supply thereafter upon request. The routine care arm (RCA) received routine postpartum contraceptive care. We asked open-ended questions about how we might maximize study retention and implemented the participants' requests in both arms.\n Our retention rate was 78%. There were three (13%) pregnancies out of 23 participants in the intervention arm and eight (30%) pregnancies out of 27 participants in the RCA. The risk of pregnancy occurring in the intervention arm was 0.57 times that of the RCA (95% CI 0.20-1.60; p=.23).\n A randomized controlled trial of postpartum teens to receive and not to receive advanced supply of EC is both feasible and necessary. Our study provides preliminary data to suggest that advanced supply of EC may help decrease repeat teen pregnancies." ]

[ "8628460", "8967757", "19029516", "9710040", "10971602", "7763202", "16426990", "15204012", "19743457" ]

[ "A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group.", "A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group.", "Subcutaneous IGF-1 is not beneficial in 2-year ALS trial.", "A placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF-I Study Group.", "Randomized controlled trial of brain-derived neurotrophic factor in Guillain-Barré syndrome: a pilot study.", "Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis.", "Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial.", "Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials.", "Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III." ]

[ "Ciliary neurotrophic factor (CNTF) is a neuroactive cytokine found in Schwann cells, which appears to be released in response to nerve injury. The ALS CNTF Treatment Study (ACTS) clinical trial was a phase II-III randomized, placebo-controlled, double-blind study designed to evaluate the safety, tolerability, and efficacy of subcutaneous administration of recombinantly produced human CNTF (rHCNTF) in slowing disease progression in 730 patients with amyotrophic lateral sclerosis (ALS). Patients were randomized to receive 30 micrograms/kg or 15 micrograms/kg rHCNTF or placebo subcutaneously three times a week for 9 months. The primary endpoint of the study, the slope of decline of isometric muscle strength in treated versus placebo patients, showed no statistically significant difference between rHCNTF and placebo-treated patients, and was complicated by an initial statistically significant decrease in strength early in rHCNTF-treated patients. Mortality was similar in all three study arms. There were no statistically significant treatment effects among the secondary measures. Side effects of rHCNTF included anorexia, weight loss, and cough and were sufficient to limit dosing in many patients.", "Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.", "Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS.\n A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used.\n There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period.\n Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis.", "To test the safety and efficacy of recombinant human insulin-like growth factor-I (rhIGF-I) in ALS, 183 patients from eight European centers were randomized to receive double-blind placebo (n = 59) or rhIGF-I 0.1 mg/kg/day (n = 124) subcutaneously for 9 months. At study completion, the primary efficacy outcome measure (change in disease progression as assessed by the Appel ALS rating scale) showed no significant difference between treatment groups. RhIGF-I appeared to be safe and well-tolerated.", "Brain-derived neurotrophic factor (BDNF) has the theoretical potential to protect neurones from axonal degeneration. The objective of this study was to discover whether brain-derived neurotrophic factor is safe in Guillain-Barré syndrome, and to make preliminary observations of its efficacy. This was a parallel group randomized controlled trial of subcutaneous brain-derived neurotrophic factor 25 microg/kg daily compared with placebo for up to 24 weeks or until patients could walk without aid. Six patients received brain-derived neurotrophic factor, of whom three had serious adverse events including one death. Four patients received placebo, of whom two had serious adverse events including one death. The rate and extent of recovery were similar in the two groups. This pilot study did not detect any serious adverse events attributed to brain-derived neurotrophic factor treatment.", "Free radicals may play a role in the pathogenesis of amyotrophic lateral sclerosis.\n To investigate the efficacy of the free radical scavenging agent acetylcysteine in patients with amyotrophic lateral sclerosis.\n Randomized, double-blind, placebo-controlled clinical trial to assess the effect of treatment with acetylcysteine on survival and disease progression.\n A university hospital referral setting.\n One hundred ten consecutive patients who fulfilled the diagnostic criteria for amyotrophic lateral sclerosis, followed up at monthly intervals for 12 months.\n Acetylcysteine or placebo in a dose of 50 mg/kg per day subcutaneously for 12 months.\n Survival.\n After 12 months, 35 patients (65%) treated with acetylcysteine and 30 (54%) given placebo were still alive (hazard ratio, 0.74 in the acetylcysteine group relative to the placebo group; 95% confidence interval, 0.41 to 1.33; log-rank test, P = .31). Rates of disease progression, as expressed by decline in muscle strength, pulmonary function, disability, and bulbar function were similar in both groups. In the subgroup of 81 patients with limb onset of the disease, 28 patients (74%) in the acetylcysteine group and 22 (51%) in the placebo group survived 12 months (hazard ratio, 0.50; 95% confidence interval, 0.24 to 1.04; P = .06). In the bulbar subgroup of 29 patients, seven patients (44%) receiving acetylcysteine and eight (62%) receiving placebo were alive at the end of the study (hazard ratio, 1.66; 95% confidence interval, 0.56 to 4.99; P = .36).\n In this trial, treatment with the free radical scavenger acetylcysteine did not result in a major increase in 12-month survival or a reduction in disease progression in patients with amyotrophic lateral sclerosis.", "Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial.\n 92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (T(i)MCS and T(i)sym) and mean improvement (microMCS and microsym) were measured.\n NIV improved T(i)MCS, T(i)sym, microMCS, microsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0.006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including microsym (p=0.018), but conferred no survival benefit.\n In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.", "Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal motor neuron disease. We carried out two randomized, double-blind, placebo-controlled, multi-centre, multi-national studies with xaliproden (a drug with neurotrophic effect) to assess drug efficacy and safety at two doses. Patients with clinically probable or definite ALS of more than 6 months and less than 5 years duration were randomly assigned to placebo, 1 mg or 2 mg xaliproden orally once daily as monotherapy in Study 1 (n=867); or to the same regimen with addition of riluzole 50 mg bid background therapy in Study 2 (n=1210 patients). The two primary endpoints were defined as: 1. Time to death, tracheostomy, or permanent assisted ventilation (DTP), and 2. Time to vital capacity (VC)<50% or DTP before (log-rank test) and after adjustment using a Cox proportional hazard model for prespecified prognostic factors. Secondary endpoints were rates of change of various functional measures. In Study 1, primary outcome measures did not reach statistical significance. For the 2 mg group, for time to VC<50% analysis (without DTP) a significant 30% RRR was obtained (95% confidence interval [CI]: 8.46, P=0.009). In Study 2, no significant results were obtained. However, there was a trend in favour of add-on 1 mg dose xaliproden vs. placebo (RRR 15% [-6.31, ns] for time to VC<50%; RRR 12% [CI: -6.27, ns] for time to VC<50% or DTP). Adjusted RR ratios were consistently more favourable for the xaliproden groups. Tolerability was good, and dose-dependent side effects were largely associated with the serotonergic properties of xaliproden. An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.", "Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative diseases other than ALS. Our aims were to choose between two high doses of CoQ10 for ALS, and to determine if it merits testing in a Phase III clinical trial.\n We designed and implemented a multicenter trial with an adaptive, two-stage, bias-adjusted, randomized, placebo-controlled, double-blind, Phase II design (n = 185). The primary outcome in both stages was a decline in the ALS Functional Rating Scale-revised (ALSFRSr) score over 9 months. Stage 1 (dose selection, 35 participants per group) compared CoQ10 doses of 1,800 and 2,700 mg/day. Stage 2 (futility test, 75 patients per group) compared the dose selected in Stage 1 against placebo.\n Stage 1 selected the 2,700 mg dose. In Stage 2, the pre-specified primary null hypothesis that this dose is superior to placebo was not rejected. It was rejected, however, in an accompanying prespecified sensitivity test, and further supplementary analyses. Prespecified secondary analyses showed no significant differences between CoQ10 at 2,700 mg/day and placebo. There were no safety concerns.\n CoQ10 at 2,700 mg daily for 9 months shows insufficient promise to warrant Phase III testing. Given this outcome, the adaptive Phase II design incorporating a dose selection and a futility test avoided the need for a much larger conventional Phase III trial." ]

[ "12182264", "9605896", "12704016", "21783053", "8882672", "11265827", "16919803", "11236404", "19996048" ]

[ "Reducing STD and HIV risk behavior of substance-dependent adolescents: a randomized controlled trial.", "Abstinence and safer sex HIV risk-reduction interventions for African American adolescents: a randomized controlled trial.", "Reducing the sexual risk behaviors of HIV+ individuals: outcome of a randomized controlled trial.", "A clinic-based motivational intervention improves condom use among subgroups of youth living with HIV.", "Evaluation of an HIV risk reduction intervention among African-American homosexual and bisexual men.", "Schoolwide effects of a multicomponent HIV, STD, and pregnancy prevention program for high school students.", "A brief individualized computer-delivered sexual risk reduction intervention increases HIV/AIDS preventive behavior.", "Efficacy of a preventive intervention for youths living with HIV.", "Efficacy of sexually transmitted disease/human immunodeficiency virus sexual risk-reduction intervention for african american adolescent females seeking sexual health services: a randomized controlled trial." ]

[ "A randomized controlled trial assessed 3 interventions designed to increase safer sex behaviors of substance-dependent adolescents. Participants (N = 161) received 12 sessions of either a health information intervention (I only), information plus skills-based safer sex training (I + B), or the same experimental condition plus a risk-sensitization manipulation (I + M + B). The I + B and I + M + B conditions, as compared with the I only condition, (a) produced more favorable attitudes toward condoms; (b) reduced the frequency of unprotected vaginal sex; and (c) increased behavioral skill performance, frequency of condom-protected sex, percentage of intercourse occasions that were condom protected, and number of adolescents who abstained from sex. The intervention that included the risk-sensitization procedure was more resistant to decay. An unexpected finding was that the I + B and I + M + B conditions produced substantial increases in sexual abstinence.", "African American adolescents are at high risk of contracting sexually transmitted infection with human immunodeficiency virus (HIV), but which behavioral interventions to reduce risk are most effective and who should conduct them is not known.\n To evaluate the effects of abstinence and safer-sex HIV risk-reduction interventions on young inner-city African American adolescents' HIV sexual risk behaviors when implemented by adult facilitators as compared with peer cofacilitators.\n Randomized controlled trial with 3-, 6-, and 12-month follow-up.\n Three middle schools serving low-income African American communities in Philadelphia, Pa.\n A total of 659 African American adolescents recruited for a Saturday program.\n Based on cognitive-behavioral theories and elicitation research, interventions involved 8 1-hour modules implemented by adult facilitators or peer cofacilitators. Abstinence intervention stressed delaying sexual intercourse or reducing its frequency; safer-sex intervention stressed condom use; control intervention concerned health issues unrelated to sexual behavior.\n Self-reported sexual intercourse, condom use, and unprotected sexual intercourse.\n Mean age of the enrollees was 11.8 years; 53% were female and 92.6% were still enrolled at 12 months. Abstinence intervention participants were less likely to report having sexual intercourse in the 3 months after intervention than were control group participants (12.5% vs 21.5%, P=.02), but not at 6- or 12-month follow-up (17.2% vs 22.7%, P=.14; 20.0% vs 23.1%, P=.42, respectively). Safer-sex intervention participants reported significantly more consistent condom use than did control group participants at 3 months (odds ratio [OR]=3.38; 95% confidence interval [CI], 1.25-9.16) and higher frequency of condom use at all follow-ups. Among adolescents who reported sexual experience at baseline, the safer-sex intervention group reported less sexual intercourse in the previous 3 months at 6- and 12-month follow-up than did control and abstinence intervention (adjusted mean days over prior 3 months, 1.34 vs 3.77 and 3.03, respectively; P< or =.01 at 12- month follow-up) and less unprotected intercourse at all follow-ups than did control group (adjusted mean days, 0.04 vs 1.85, respectively, P<.001, at 12-month follow-up). There were no differences in intervention effects with adult facilitators as compared with peer cofacilitators.\n Both abstinence and safer-sex interventions can reduce HIV sexual risk behaviors, but safer-sex interventions may be especially effective with sexually experienced adolescents and may have longer-lasting effects.", "Testing behavioral interventions to increase safer sex practices of HIV+ individuals has the potential to significantly reduce the number of new infections. This study evaluated a behavioral intervention designed to reduce the sexual risk behaviors of HIV+individuals. HIV+individuals (N = 387) who reported engaging in unprotected sex with HIV- or partners of unknown serostatus were randomly assigned to (a) a single counseling session targeting problem areas identified by the participant in 3 possible intervention domains (i.e., condom use, negotiation, disclosure); (b) a single-session comprehensive intervention that covered all 3 intervention domains; (c) the same comprehensive intervention, plus 2 monthly booster sessions; or (d) a 3-session diet and exercise attention-control condition. The median number of unprotected sex acts decreased from 14 at baseline to 6, 6, and 4 at 4-, 8-, and 12-month follow-ups, respectively. A repeated measures analysis of variance revealed a significant decrease in unprotected sex acts across all groups across time. A significant Group x Time interaction revealed that the comprehensive-with-boosters group had the most unprotected sex at 8-month follow-up as compared to the other 3 groups. These findings suggest that a brief intervention can result in large reductions in HIV transmission risks among HIV+individuals, but the relative benefit of one intervention approach over another remains unclear.", "More than 50% of youth living with HIV (YLH) have unprotected sex. In previous studies, we reported effects of a motivational interviewing-based multirisk reduction intervention, \"Healthy Choices\" in improving motivation, depression, and viral load in YLH. In this study, we report the effect of the intervention on increasing condom use.\n Six waves of longitudinal data (n = 142) across a period from baseline through 15 months postintervention were analyzed. The developmental trajectory modeling method was used for program effect evaluation.\n The three groups detected with distinct sexual risks were: Persistent low sexual risk (PLSR), delayed high sexual risk, and high and growing sexual risk with regard to levels and time trajectories of condom use throughout the trial. Receiving Healthy Choices increased the likelihood to be in the PLSR group (63% vs. 32%, p < .01) and reduced the likelihood to be in the delayed high sexual risk group (16% vs. 50%, p < .05). Receiving the intervention was also associated with progressive reductions in no-condom sex for PLSR youth (adjusted β = -.325, p < .01) and high and growing sexual risk youth (adjusted β = -.364, p < .01).\n The motivational interviewing-based program Healthy Choices, when delivered in clinic settings, can prevent unprotected sex in subgroups of YLH, although more intensive interventions may be needed to change risk trajectories among those at highest risk of transmitting the AIDS virus. Developmental trajectory analysis provides an alternative approach to evaluate program effects for study samples that contain distinct subgroups.\n Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.", "To provide the first data which evaluates an HIV risk reduction intervention designed to reduce HIV high-risk sexual behavior in African-American homosexual and bisexual men.\n Participants (n = 318) were recruited from bars, bathhouses, and erotic bookstores, and through homosexual African-American organizations, street out-reach, media advertisements, and personal referrals of individuals aware of the study.\n Participants were randomized into a single or triple session experimental group or a wait-list control group. Both experimental interventions included AIDS risk education, cognitive-behavioral self-management training, assertion training, and attempts to develop self-identity and social support. Data collection involved assessments of self-reported changes in sexual behavior at 12- and 18-month follow-up.\n Participants in the triple session intervention greatly reduced their frequency of unprotected anal intercourse (from 46 to 20%) at the 12-month follow-up evaluation and (from 45% to 20%) at the 18-month follow-up evaluation. However, levels of risky behavior for the control group remained constant (from 26 to 23% and from 24 to 18%) at 12- and 18-month follow-up evaluations, respectively. In addition, levels of risky behavior for the single session intervention decreased only slightly (from 47 to 38% and from 50 to 38%) at the 12- and 18-month follow-up evaluations, respectively.\n Results were interpreted to demonstrate the superiority of a triple session over a single session intervention in reducing risky sexual behavior in this cohort.", "Few studies have tested schoolwide interventions to reduce sexual risk behavior, and none have demonstrated significant schoolwide effects. This study evaluates the schoolwide effects of Safer Choices, a multicomponent, behavioral theory-based HIV, STD, and pregnancy prevention program, on risk behavior, school climate, and psychosocial variables. Twenty urban high schools were randomized, and cross-sectional samples of classes were surveyed at baseline, the end of intervention (19 months after baseline), and 31 months afterbaseline. At 19 months, the program had a positive effect on the frequency of sex without a condom. At 31 months, students in Safer Choices schools reported having sexual intercourse without a condom with fewer partners. The program positively affected psychosocial variables and school climate for HIV/STD and pregnancy prevention. The program did not influence the prevalence of recent sexual intercourse. Schoolwide changes in condomuse demonstrated that aschool-based program can reduce the sexual risk behavior of adolescents.", "One objective of translational science is to identify elements of human immunodeficiency virus (HIV) risk-reduction interventions that have been shown to be effective and find new ways of delivering these interventions to the community to ensure that they reach the widest possible audience of at-risk individuals. The current study reports the development and evaluation of a computer-delivered, theory-based, individually tailored HIV risk-reduction intervention.\n This study evaluated the effectiveness of a custom computerized HIV/AIDS risk reduction intervention at increasing HIV/AIDS preventive behaviors in a randomized trial with 157 college students. The intervention content and delivery were based on the Information-Motivation-Behavioral Skills Model of Health Behavior Change and used Motivational Interviewing techniques. Participants completed a baseline assessment of HIV prevention information, motivation, behavioral skills and behavior, attended two brief computer-delivered intervention sessions, and completed a follow-up assessment.\n As compared to the control group (a nutrition education tutorial), participants who interacted with the computer-delivered HIV/AIDS risk reduction intervention exhibited a significant increase in risk reduction behavior. Specifically, participants reported a greater frequency of keeping condoms available and displayed greater condom-related knowledge at a four-week follow-up session; among sexually active participants, there was a significant increase in self-reported condom use.\n Delivery of brief individually tailored HIV/AIDS risk reduction interventions via computer may be an effective HIV/AIDS prevention approach for adolescents. More research is needed to further support the effectiveness of this type of intervention and determine the generalizability of these findings to economically and educationally disadvantaged adolescents.", "HIV transmission behaviors and health practices of HIV-infected youths were examined over a period of 15 months after they received a preventive intervention.\n HIV-infected youths aged 13 to 24 years (n = 310; 27% African American, 37% Latino) were assigned by small cohort to (1) a 2-module (\"Stay Healthy\" and \"Act Safe\") intervention totaling 23 sessions or (2) a control condition. Among those in the intervention condition, 73% attended at least 1 session.\n Subsequent to the \"Stay Healthy\" module, number of positive lifestyle changes and active coping styles increased more often among females who attended the intervention condition than among those in the control condition. Social support coping also increased significantly among males and females attending the intervention condition compared with those attending the control condition. Following the \"Act Safe\" module, youths who attended the intervention condition reported 82% fewer unprotected sexual acts, 45% fewer sexual partners, 50% fewer HIV-negative sexual partners, and 31% less substance use, on a weighted index, than those in the control condition.\n Prevention programs can effectively reduce risk acts among HIV-infected youths. Alternative formats need to be identified for delivering interventions (e.g., telephone groups, individual sessions).", "To evaluate the efficacy of an intervention to reduce incident sexually transmitted disease (STD) and enhance STD/human immunodeficiency virus (HIV)-preventive behaviors and psychosocial mediators.\n A randomized controlled trial of an HIV prevention program.\n Clinic-based sample in Atlanta, Georgia.\n African American adolescent females (N = 715), aged 15 to 21 years, seeking sexual health services. Participants completed an audio computer-assisted self-interview and provided self-collected vaginal specimens for STD testing. Intervention Intervention participants received two 4-hour group sessions and 4 telephone contacts over a 12-month period, targeting personal, relational, sociocultural, and structural factors associated with adolescents' STD/HIV risk, and were given vouchers facilitating male partners' STD testing/treatment. Main Outcome Measure Incident chlamydial infections.\n Over the 12-month follow-up, fewer adolescents in the intervention had a chlamydial infection (42 vs 67; risk ratio [RR], 0.65; 95% confidence interval [CI], 0.42 to 0.98; P = .04) or recurrent chlamydial infection (4 vs 14; RR, 0.25; 95% CI, 0.08 to 0.83; P = .02). Adolescents in the intervention also reported a higher proportion of condom-protected sex acts in the 60 days preceding follow-up assessments (mean difference, 10.84; 95% CI, 5.27 to 16.42; P < .001) and less frequent douching (mean difference, -0.76; 95% CI, -1.15 to -0.37; P = .001). Adolescents in the intervention were also more likely to report consistent condom use in the 60 days preceding follow-up assessments (RR, 1. 41; 95% CI, 1.09 to 1.80; P = .01) and condom use at last intercourse (RR, 1.30; 95% CI, 1.09 to 1.54; P = .005). Intervention effects were observed for psychosocial mediators of STD/HIV-preventive behaviors.\n Interventions for African American adolescent females can reduce chlamydial infections and enhance STD/HIV-preventive behaviors and psychosocial mediators of STD/HIV-preventive behaviors. Trial Registration clinicaltrials.gov Identifier: NCT00633906." ]

[ "6437487", "7660408", "17335327", "1998929", "9407576", "8357287", "8185149", "10404919", "11509308" ]

[ "Day hospital rehabilitation--effectiveness and cost in the elderly: a randomised controlled trial.", "Outcomes of elderly stroke patients. Day hospital versus conventional medical management.", "Are day hospitals effective for acutely ill psychiatric patients? A European multicenter randomized controlled trial.", "Effectiveness of a geriatric day hospital.", "A randomized trial of geriatric liaison intervention in elderly medical inpatients.", "A negative trial of inpatient geriatric consultation. Lessons learned and recommendations for future research.", "Comprehensive discharge planning for the hospitalized elderly. A randomized clinical trial.", "Chronic care clinics: a randomized controlled trial of a new model of primary care for frail older adults.", "Stroke rehabilitation after hospital discharge: a randomized trial comparing domiciliary and day-hospital care." ]

[ "The effectiveness and cost of day hospital care in rehabilitation were studied in a randomised controlled trial in 120 elderly patients who were assessed at referral and six weeks and five months later in activities of daily living skills and mood. Day hospital patients were compared with a control group, who were managed as they would have been before the availability of day hospital care. Day hospital patients showed a significant improvement in performance of activities of daily living at six weeks but not at five months; however, they had a sustained improvement in mood. The cost of day hospital rehabilitation was one third greater than that of rehabilitation by alternative means. In its current form the geriatric day hospital is not a cheap alternative to other means of rehabilitation. Expensive components of the day hospital should be critically re-examined and renewed emphasis placed on sufficient inpatient beds, domiciliary services, and day care centres.", "Much controversy exists over the value of geriatric day hospitals in the rehabilitation of elderly patients, and cerebrovascular accident is a particularly common diagnosis among patients referred to these day hospitals. We carried out a prospective, randomized study to compare the outcomes of elderly stroke patients managed by a geriatric team using a day hospital facility versus conventional medical management.\n One hundred twenty elderly patients with acute stroke were randomized to inpatient care on a stroke ward under the care of either a neurologist or a geriatric team. Those under the care of neurologists were hospitalized until the attending physician felt that the patients had reached full rehabilitation potential. Patients under the care of the geriatric team were discharged home as soon as the team felt they were able to cope and given follow-up rehabilitation at the day hospital. Family or community support was arranged when necessary for both treatment groups. On recruitment, patient demographics, medical history, clinical features related to stroke, and functional ability as measured by the Barthel Index were noted. Subjects were reviewed at 3 and 6 months to assess functional level, hospital and outpatient services received, general well-being, mood, and level of satisfaction. Costs of treatment of the two groups were also compared.\n Functional improvement (Barthel Index score) was greater in the group managed by the geriatricians with a day hospital facility compared with the conventional group at 3 months (P = .03). There were also fewer outpatient visits among the day hospital patients at 6 months (P = .03). No significant difference was found in costs between the two treatment groups.\n Compared with conventional medical management, care in the geriatric day hospital hastened functional recovery and reduced outpatient visits in elderly stroke patients without additional cost.", "Acute psychiatric day care has been proposed as an alternative to conventional inpatient care, yet the evidence of its effectiveness is inconsistent and based only on single-site studies in 3 countries. The aim of this multicenter randomized controlled trial was to establish the effectiveness of acute day hospital care in a large sample across a range of mental health care systems.\n The trial was conducted from December 2000 to September 2003 in 5 European countries, with a sample of 1117 voluntarily admitted patients. Immediately before or very shortly after admission to the participating psychiatric facilities, patients were randomly allocated to treatment in a day hospital or an inpatient ward. Psychopathology, treatment satisfaction, subjective quality of life, and social disabilities were assessed at admission, at discharge, and 3 and 12 months after discharge. An intention-to-treat analysis was conducted using fixed-effects linear models with structured error covariance matrices and covariates.\n Day hospital care was as effective as conventional inpatient care with respect to psychopathologic symptoms, treatment satisfaction, and quality of life. It was more effective on social functioning at discharge and at the 3- and 12-month follow-up assessments.\n This study, which has more than doubled the existing evidence base, has shown that day hospital care is as effective on clinical outcomes as conventional inpatient care and more effective on social outcomes.\n ClinicalTrials.gov identifier NCT00153959.", "To determine whether there is a difference in the quality of life between elderly patients managed in a day hospital and those receiving conventional care.\n Randomized controlled trial; assessment upon entry to study and at 3, 6 and 12 months afterward.\n Geriatrician referral-based secondary care.\n A total of 113 consecutively referred elderly patients with deteriorating functional status believed to have rehabilitation potential; 55 were assessed and treated by an interdisciplinary team in a day hospital (treatment group), and 58 were assessed in an inpatient unit or an outpatient clinic or were discharged early with appropriate community services (control group).\n Barthel Index, Rand Questionnaire, Global Health Question and Geriatric Quality of Life Questionnaire (GQLQ).\n Eight study subjects and four control subjects died; the difference was insignificant. Functional status deteriorated over time in the two groups; although the difference was not significant there was less deterioration in the control group. The GQLQ scores indicated no significant difference between the two groups in the ability to perform daily living activities and in the alleviation of symptoms over time but did show a trend favouring the control group. The GQLQ scores did indicate a significant difference in favour of the control group in the effect of treatment on emotions (p = 0.009).\n The care received at the day hospital did not improve functional status or quality of life of elderly patients as compared with the otherwise excellent geriatric outpatient care.", "The aim of this study was to examine the effect of psychogeriatric intervention in a group of elderly medical inpatients over 75 years of age. In addition to usual care, intervention consisted of multidisciplinary joint treatment by a psychogeriatric team. The main purpose of intervention was to obtain the optimal level of physical functioning.\n In a prospective randomized trial the effect of the intervention (N = 140) compared with usual care (N = 97) was estimated for physical functioning, length of stay, and nursing home placement within 12 months of discharge.\n Substantially more patients assigned to the intervention group improved in their physical functioning, and fewer became worse. The mean length of stay was 5 days shorter for the intervention group. There were more readmissions to hospital in the usual care group (29.9%) compared with the intervention group (17.4%). Of the patients assigned to the intervention treatment, 18% were admitted to a nursing home. In the usual care group this was 27%. The effects of intervention remained statistically significant for all the outcome variables after controlling for possible confounding baseline characteristics.\n The intervention we studied had clinically relevant effects on important outcome variables. Psychiatric co-morbidity was an important risk factor for the outcome of the patients in our study. By combining elements from a psychiatric and geriatric consultation service with elements from a unit-driven service, we were able to improve health care for the elderly in our hospital in a feasible and cost-effective way.", "To determine the effectiveness of inpatient interdisciplinary geriatric consultation provided during hospitalization to frail, elderly subjects. SUBJECTS AND SITE: Admission cohort of 197 men admitted from 1985 through 1989, aged 65 years or more, meeting proxy criteria for frailty, living within follow-up area, without terminal illness, and without prolonged nursing home residence.\n Randomized controlled trial of inpatient geriatric consultation at a tertiary care Veterans Affairs hospital. Differences were determined between groups in the Physical Self-Maintenance Scale, Instrumental Activities of Daily Living, Mini-Mental State Examination, Morale Scale, and nursing home and health care utilization.\n No differences were seen between groups in any measure after the intervention or during 1 year of follow-up. Intervention implementation may have been incomplete due to compliance and resource availability.\n This trial is not definitive in determining whether geriatric consultation is effective or ineffective. Lessons learned from this research indicate that future studies should target frail subjects, include intervention-specific measures, and be conducted with direct control of comprehensive resources.", "To study the effects of a comprehensive discharge planning protocol, designed specifically for the elderly and implemented by nurse specialists, on patient and caregiver outcomes and cost of care.\n Randomized clinical trial.\n Hospital of the University of Pennsylvania.\n 276 patients and 125 caregivers. Patients were 70 years and older and were placed in selected medical and surgical cardiac diagnostic-related groups.\n Group differences in patient outcomes (length of initial hospital stay, length of time between initial hospital discharge and readmission, and rehospitalization rates) and charges for care (charges for initial hospitalization, rehospitalizations, health services after discharge, and nurse specialist services) were measured 2, 6, and 12 weeks after discharge.\n From the initial hospital discharge to 6 weeks after discharge, patients in the medical intervention group had fewer readmissions, fewer total days rehospitalized, lower readmission charges, and lower charges for health care services after discharge. No differences in these outcomes were found between the surgical intervention and control groups during this period.\n Study findings support the need for comprehensive discharge planning designed for the elderly and implemented by nurse specialists to improve their outcomes after hospital discharge and to achieve cost savings. The findings also suggest that this intervention had its greatest effect in delaying or preventing rehospitalization of patients in the medical intervention group during the first 6 weeks after discharge.", "To determine whether a new model of primary care, Chronic Care Clinics, can improve outcomes of common geriatric syndromes (urinary incontinence, falls, depressive symptoms, high risk medications, functional impairment) in frail older adults.\n Randomized controlled trial with 24 months of follow-up. Physician practices were randomized either to the Chronic Care Clinics intervention or to usual care.\n Nine primary care physician practices that comprise an ambulatory clinic in a large staff-model HMO in western Washington State.\n Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline.\n Intervention practices (5 physicians, 96 patients) held half-day Chronic Care Clinics every 3 to 4 months. These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications; and a patient self-management/support group. Control practices (4 physicians, 73 patients) received usual care.\n Changes in self-reported urinary incontinence, frequency of falls, depressive symptoms, physical function, and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences, covariates, and practice-level variation. Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed.\n After 24 months, no significant improvements in frequency of incontinence, proportion with falls, depression scores, physical function scores, or prescriptions for high risk medications were demonstrated. Costs of medical care including frequency of hospitalization, hospital days, emergency and ambulatory visits, and total costs of care were not significantly different between intervention and control groups. A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients (40.0% vs 25.3%, P = .10).\n Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics, improved outcomes for selected geriatric syndromes were not demonstrated. These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system.", "To compare the effectiveness and costs of a new domiciliary rehabilitation service for elderly stroke patients with geriatric day-hospital care.\n Randomized controlled trial.\n Stroke patients aged 55+ who required further rehabilitation after hospital discharge or after referral to geriatricians from the community.\n Poole area, East Dorset, a mixed urban/rural area on the south coast of England.\n Primary-changes between hospital discharge and 6-month follow-up in physical function as measured by Barthel index. Secondary-changes over this period in Rivermead Mobility Index and mental state (Philadelphia Geriatric Centre Morale Scale) and differences in social activity (Frenchay Activities Index) and generic health status (SF-36). Health service and social service cost per patient were compared for the two groups.\n 180 patients were eligible and 140 (78%) were randomized. The groups were well balanced for age, sex, social class and initial Barthel index. We achieved follow-up in 88% of subjects who were alive at 6 months. We detected no significant differences in patient outcomes, although there was a non-significant improvement in measures of physical function and social activity in the domiciliary group. Domiciliary patients had more physiotherapy time per session and more district nurse time, and made greater use of social service day centres and home helps. Total cost per patient did not differ significantly between the two groups, with reduced health service costs in the domiciliary arm offset by higher social service costs.\n No significant differences were detected in the effectiveness of the two services. Neither service influenced patients' mental state, and their social activity remained low. Total costs were similar. A mixed model of day-hospital and domiciliary care may be most cost-effective for community stroke rehabilitation, but this requires further evaluation." ]

[ "12835516", "8410110", "17308269", "16325695", "3881176", "3909798", "3047339", "2897433", "324620" ]

[ "Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882): an Eastern Cooperative Oncology Group study.", "Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party.", "Sequenced compared with simultaneous anthracycline and cyclophosphamide in high-risk stage I and II breast cancer: final analysis from INT-0137 (S9313).", "Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial.", "Randomized trial of combination chemotherapy in hormone-resistant metastatic prostate carcinoma.", "Randomized clinical trial of doxorubicin alone or combined with mitolactol in women with advanced breast cancer and prior chemotherapy exposure.", "Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity.", "Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial.", "Evaluation of single-drug versus multiple-drug chemotherapy in the treatment of advanced breast cancer." ]

[ "This study, a phase III multicenter randomized trial opened by ECOG in April 1983 and closed in June 1986 was designed to evaluate whether a combination of doxorubicin and an intravenous formulation of diethylstilbestrol diphosphate (DES) was superior to doxorubicin alone in men with hormone refractory prostate cancer. All patients received doxorubicin at a dose of 50 mg/m2 iv every 3 wk either alone or with 1 g DES iv daily for 5 d followed by 1 g iv twice weekly for four cycles (12 wk). The 51 evaluable patients with visceral metastases displayed a significantly increased response rate (27% vs 63%) on the combined therapy arm (p = 0.04). However, the 111 evaluable patients with osseous disease exhibited no difference in response rate between either arm with a p-value of >0.99. Similarly, clinical response rates revealed no difference between the two arms. Cases of cardiac toxicity graded as severe, life threatening, or lethal in the combined therapy arm were 10 times more frequent in the combined-therapy arm than in the doxorubicin-alone group (6.75% compared to 0.7%). This difference was statistically significant (p = 0.0041). All of the cases of superficial and deep venous thrombosis occurred on the combined-therapy arm. There were no other significant differences in the numbers of grade 3 or 4 toxic events. The most common toxicity was hematologic. Failure-free survival duration did reach statistical significance in the combined-therapy group (p = 0.012), although the actual durations were short (2.6-3.2 mo). There was no difference in overall survival between the two groups.", "A randomized trial was conducted in patients with small-cell lung cancer (SCLC) to determine if survival can be improved by a weekly chemotherapy regimen combining various drugs.\n Two hundred twenty-three patients were randomized to receive either six courses of a multiple-drug combination (MDC) regimen (Adriamycin [ADR; doxorubicin; Farmitalia Carlo Erba, Milan, Italy] 25 mg/m2 intravenously [i.v.] on day 1; etoposide [VP16] 120 mg/m2 i.v. on day 1; cyclophosphamide [CPA] 500 mg/m2 i.v. on day 1; cisplatin 60 mg/m2 i.v. on day 8; vindesine [VDS] 3 mg/m2 i.v. on day 8; vincristine [VCR] 2 mg i.v. on day 15; methotrexate [MTX] 100 mg/m2 i.v. on day 15), or a standard chemotherapy (SC) regimen (ADR 50 mg/m2 i.v. on day 1; CPA 1 g/m2 i.v. on day 1; VP16 80 mg/m2 i.v. on days 1 to 3).\n In 98 MDC-treated and 101 SC-treated assessable patients, we observed 69% and 62% objective responses rates, respectively. There was no significant difference in survival, with median durations and 2-year overall survival rates of 49 and 43 weeks and 8.5% and 7.9%, respectively. There was a significant increase in response rate in favor of MDC patients with limited disease (84% v 62%). Toxicity was tolerable, although SC was more hematotoxic, with 76% (v 59%) experiencing leukopenia and 17% (v 7%) experiencing thrombocytopenia (grades III and IV). If the cumulative doses received were nearly equal to the scheduled cumulative doses in both arms, the total relative dose-intensity (RDI) was significantly higher in the SC arm. The difference was due to increased treatment delays in the MDC arm.\n Weekly MDC failed to improve survival rates in patients with SCLC.", "We conducted a phase III randomized study of two adjuvant treatment schedules of doxorubicin (A) and cyclophosphamide (C) in early-stage breast cancer to determine if administration of sequential single agents (A --> C) results in superior disease-free survival (DFS) and overall survival (OS) versus the same total dose given in combination (AC).\n High-risk node-negative or low-risk node-positive breast cancer patients received AC given: (arm I) concurrently (AC) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously (IV) every 3 weeks for six cycles; or (arm II) in sequence (A C) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cycles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles. Total dose and duration were identical, but the intensity of each drug was increased on A C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics. All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy.\n Between 1994 and 1997, 3,176 patients were randomly assigned. Arms were well balanced; 48% of eligible patients were node-negative and 48% were estrogen receptor-positive. No significant differences in OS or DFS were observed; 5-year estimates of OS (95% CI) were 88% (87% to 90%) on AC and 89% (87% to 91%) on A --> C. Grade 4 hematologic toxicity was greater on A --> C, but nonhematological grade 4 was similar.\n The overall result does not support superiority of dose-intense sequenced single agents. The greater toxicity of higher doses of single agents does not support their sequential use.", "Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment. In trials with historical controls, high-dose chemotherapy produced improved outcomes. We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial.\n Patients with at least nine positive nodes were randomly assigned either two courses of accelerated (2-week intervals, with filgrastim support), conventionally dosed epirubicin and cyclophosphamide followed by two courses of high-dose chemotherapy (epirubicin, cyclophosphamide, and thiotepa supported by peripheral-blood progenitors) or four identical cycles of epirubicin and cyclophosphamide followed by three cycles of accelerated cyclophosphamide, methotrexate, and fluorouracil. The primary endpoint was event-free survival. Analyses were done both by intention to treat and per protocol.\n 403 patients were enrolled; 201 were assigned high-dose chemotherapy and 202 conventional treatment. The mean number of positive nodes was 17.6, and median follow-up was 48.6 months. 4-year event-free survival (intention-to-treat analysis) was 60% (95% CI 53-67) in the high-dose chemotherapy group and 44% (37-52) in the control group (p=0.00069). The corresponding overall survival was 75% (69-82) versus 70% (64-77; p=0.02). There were no treatment-related deaths.\n Our finding of significant improvements in both event-free and overall survival for high-dose chemotherapy compared with a dose-dense conventional regimen contrasts with the results of other studies. The discrepancy might be due partly to design differences (tandem, brief induction) between our regimen and those studied in other trials. This approach merits further study.", "A prospective randomized study was conducted in 51 patients with stage D hormone-resistant prostatic carcinoma, comparing a combination of doxorubicin and lomustine (DC) with cyclophosphamide and 5-FU (CF). Patients were assessed objectively (employing National Prostate Cancer Project criteria) and subjectively (using a numerical scoring scheme). Each regimen was well tolerated with acceptable levels of myelosuppression. The objective partial response rate was 57% for DC and 8% for CF. Objective stabilization occurred, respectively, in 14% and 44% of the patients. Similarly, DC demonstrated a significantly superior subjective response rate (partial plus complete) of 82%, compared to 48% for CF. Patients with poor initial performance status or liver involvement had significantly lower response rates and reduced survival. Overall, there was no significant difference in survival between the two arms, reflecting the similarity between DC and CF in total objective response rate (partial response plus stable disease). DC provided superior palliation and was well tolerated by an essentially geriatric population.", "One hundred fifty-one women with advanced breast cancer who had failed prior chemotherapy were randomized to monthly courses of doxorubicin (60 mg/m2 I.V. day 1, observation after 500 mg/m2) or doxorubicin (40 mg/m2 I.V. day 1; maximum 500 mg/m2) and mitolactol (135 mg/m2 orally, days 1-10; 180 mg/m2 after maximum doxorubicin). Median survival times were 232 days for doxorubicin and 225 days for doxorubicin + mitolactol, and median times to progression were 112 days and 97 days, respectively. Results are inconsistent with a 25% improvement in survival or time to progression for doxorubicin + mitolactol (p = 0.04 and 0.02, respectively, adjusted for stratification factors but not multiple testing). Regression rates for all patients, both measurable and evaluable, were 30% for doxorubicin alone and 26% for doxorubicin + mitolactol. Regression rates were significantly higher in patients with measurable indicator lesions. Cardiac toxicity was seen in four patients, all of whom were receiving doxorubicin alone. It appears that the combination of doxorubicin + mitolactol is not substantially more effective than doxorubicin alone in women with advanced breast cancer and prior chemotherapy exposure.", "We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen.", "From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.", "Fifty-one postmenopausal patients with advanced breast cancer were randomized to receive either cyclophosphamide given continuously or cyclophosphamide given continuously with methotrexate, 5-fluorouracil, vincristine, and prednisone given intermittently. The results with the multiple-drug therapy were significantly better than with the single-drug therapy, both with regard to percentage (63% versus 25%) and median duration (400 versus 210 days) of objective response. Toxicity was moderately increased with the combination as compared to the single-drug treatment." ]

[ "7843707", "8780576", "7762065", "8605558", "10693639", "11477342", "11389707", "12297843", "8475558" ]

[ "A double-blind, randomized, placebo-controlled trial of prostaglandin E1 in liver transplantation.", "Prostaglandin E1 administration following orthotopic liver transplantation: a randomized prospective multicenter trial.", "Enisoprost in liver transplantation.", "Postoperative intravenous infusion of alprostadil (PGE1) does not improve renal function in hepatic transplant recipients.", "Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial.", "The effects of lipid-lowering agents on acute renal allograft rejection.", "Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection.", "Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.", "Evidence that intraoperative prostaglandin E1 infusion reduces impaired platelet aggregation after reperfusion in orthotopic liver transplantation." ]

[ "A double-blind placebo-controlled trial of intravenous prostaglandin PGE1 (40 micrograms/h) was conducted in adult orthotopic liver transplant recipients. Infusion was started intraoperatively and continued for up to 21 days. Patients were followed up for 180 days postoperatively. Among 172 patients eligible for treatment in the study, 160 could be evaluated (78 PGE1; 82 placebo). Patient and graft survival were similar (PGE1: 16 deaths, 9 retransplantations [7 survivors]; controls: 15 deaths, 6 retransplantations [3 survivors]). In patients with surviving grafts, however, PGE1 administration resulted in a 23% shorter mean duration of hospitalization following transplantation (PGE1: 24.4 days; controls: 31.8 days; P = .02) and a 40% shorter length of time postoperatively in the intensive care unit (PGE1: 8.2 days; controls 13.7 days; P = .05). Reduced needs for renal support (P = .03) or surgical intervention other than retransplantation (P = .02) were also noted with PGE1 use. Further, PGE1 administration resulted in a trend toward improved survival rates in patients with mild renal impairment (preoperative serum creatinine 1.5 mg percent or greater; P = .08). Neither the incidence of acute cellular rejection nor of primary nonfunction was significantly different in the two groups. Phlebitis was the only complication that was more common during PGE1 administration, (PGE1: 9; controls: 4). These results suggest that PGE1 use in hepatic allograft recipients reduces morbidity and may result in sizable cost reductions.", "Prostaglandin E1 (PGE1) has been used after orthotopic liver transplantation (OLT) based on limited clinical data suggesting PGE1 infusion improves immediate hepatic allograft function. The aim of this study was to conduct a randomized double-blinded multicenter trial to evaluate the effect of PGE1 on early hepatic and renal function in patients undergoing OLT.\n One hundred eighteen patients were randomized to receive either PGE1 or crystalloid placebo intravenously after allograft revascularization. Primary end points were incidence of primary allograft nonfunction (PNF) or severe renal dysfunction.\n The incidence of PNF was 6.7% (4 of 60) and 6.9% (4 of 58) in the control and PGE1 groups, respectively. PGE1 infusion was, however, associated with improved early renal function (mean peak creatinine level of 1.4 +/- 1.0 and 2.0 +/- 1.0 in patients treated with PGE1 and placebo, respectively; P < 0.001). Severe renal dysfunction occurred more frequently in the placebo group (26.7%) than in the PGE1 group (13.8%; P = 0.65). Additionally, dialysis treatments were more frequent in the placebo group (0.7 +/- 2.0 per patient) than in the PGE1 group (0.2 +/- 1.0 per patient; P = 0.10). Initial intensive care unit stay was shorter in patients treated with PGE1 (4.0 +/- 3.6 days) compared with controls (10.5 +/- 17.1 days) (P < 0.01).\n PGE1 administration after OLT resulted in improved renal function and decreased initial postoperative intensive care unit stay but did not affect the incidence of PNF.", "Previous human studies in renal transplant recipients have shown a lower incidence of acute rejection and cyclosporine-associated acute nephrotoxicity when prostaglandins are administered in conjunction with standard immunosuppressants. This study evaluates the effects of enisoprost (EP), a synthetic PGE methyl ester analog, in a single-center, prospective, randomized, double-blind, placebo-controlled, parallel group trial in 81 consecutive adult patients undergoing orthotopic liver transplantation (OLT). The subjects received EP 100 mg p.o. t.i.d. (n = 40) or placebo (n = 41) for the first 12 weeks after OLT. Immunosuppression was based on cyclosporine, azathioprine, and corticosteroids. Effective renal plasma flow and glomerular filtration rate were determined at 4 and 12 weeks after OLT. Eighty-one patients entered the study; sixty-six patients completed the 16-week study period. There were no statistically significant differences between EP- and placebo-treated groups at 12 weeks for creatinine clearance, glomerular filtration rate, and effective renal plasma flow. At least 1 episode of cyclosporine nephrotoxicity occurred in 7/40 patients (17.5%) in the EP group compared with 9/41 patients (20.0%) in the placebo group (P = 0.781). There was no significant difference in the incidence of graft rejection episodes in the 2 groups. Enisoprost, as used in this study, does not have any beneficial effect on renal function or incidence of rejection in OLT recipients.", "Acute renal failure is a frequent complication following orthotopic hepatic transplantation. A reduction in the synthesis of intrarenal vasodilator prostaglandins has been proposed as having an important role in the pathogenesis of renal insufficiency associated with hepatic dysfunction, as well as in the nephrotoxicity associated with cyclosporine and FK506 immunosuppressive therapy. Therefore, administration of vasodilator prostaglandins may improve renal function following hepatic transplantation. This study was designed to determine the effect of continuous intravenous alprostadil (prostaglandin E1) on postoperative renal function in hepatic transplant patients.\n In a randomized, double-blind, placebo-controlled trial, 21 patients who had undergone orthotopic hepatic transplantation and had a measured postoperative glomerular filtration rate (GFR) of less that 50 mL/minute received intravenous alprostadil at 0.6 microgram/kg/hour or placebo for five days. Glomerular filtration rate and effective renal plasma flow (ERPF) were measured by a single-injection clearance method using a radionuclide agent in 53 patients within 12 hours after admission to our surgical intensive care unit. Usual postoperative care was not modified. Radionuclide GFR and ERPF measurements were repeated on postoperative day 3. Serum creatinine was measured preoperatively and postoperatively on day 3 and on day 5. A 24-hour serum creatinine clearance was measured on days 1, 5, and 14. Urine output was recorded hourly during the infusion period.\n Ten patients received alprostadil, and 11 patients received placebo. There was a significant increase in GFR and ERPF in both groups on post-operative day 3 as compared with baseline values. There was no difference in GFR and ERPF between the two groups on day 3 (48 +/- 18 and 246 +/- 68 mL/minute in the alprostadil group compared with 53 +/- 17 and 270 +/- 131 mL/minute in the placebo group). Serum creatinine levels increased on day 3 in both groups but returned to baseline by day 5.\n These results indicate that a reversible decrease in GFR is common on hepatic transplant patients during the postoperative period. Administration of a continuous intravenous infusion of alprostadil in the immediate postoperative period had no effect on renal function when compared with placebo.", "The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT. A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n = 15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary-artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (deltaO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively. A significant correlation between deltaO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p < 0.05). PGI2 treatment induced a significant decrease in deltaO2 after 24 and 48 h after reperfusion (p < 0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418 +/- 99 vs. 638 +/- 156 U/L, p < 0.1). These results suggest that administration of PGI2 after OLT improves hepatic-splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.", "Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown.\n Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52).\n Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study.\n Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.", "3-Hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitors are established anti-lipidemic agents. They also exert immunomodulatory effects. Two recent reports suggest that pravastatin may be useful in decreasing the incidence and severity of acute rejections (ARs) in heart and kidney transplant recipients. We undertook this prospective, randomized, placebo-controlled, double blind trial to investigate the effect of lovastatin on acute renal allograft rejection. Sixty-five consecutive, one-haplotype-matched, living related first renal transplant recipients were randomized to receive either lovastatin 20 mg/d or placebo for 3 months, in addition to cyclosporine, azathioprine, and steroids. Lipid levels, AR episodes, and liver and muscle enzymes were followed for 3 months post-transplant. At the end of the study period, lovastatin had successfully controlled lipid levels. However, there was no effect on AR episodes (15.15% in the treatment group vs. 18.75% in the placebo group).", "Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.", "Recent investigations measuring platelet aggregation during 10 orthotopic liver transplantations showed a significant decrease in platelet aggregation immediately after reperfusion and in the perfusate. As prostaglandin E1 has been shown to exhibit a beneficial effect in the treatment of ischemic injury of the liver, we investigated in a prospective, randomized, and open study the effect of PGE1 infusion during OLT on platelet function. Ten patients were randomized to receive a continuous PGE1 infusion (PG group) and another ten patients served as controls. Platelet function was determined ex vivo by measuring the adenosine diphosphate-, collagen-, and ristocetin-induced aggregation in platelet-rich plasma. A significantly higher platelet aggregability was measured in the PG group throughout the whole operation for ADP (1 and 2 mumol/L) and collagen (0.5 micrograms/ml). The same was true for collagen (1 microgram/ml) and ristocetin (1.2 mg/ml) after reperfusion. Not only the postreperfusional decrease in platelet aggregation but also the decline in platelet count that occurred in the control group could be prevented greatly by PGE1 infusion. In the perfusate, released from the liver graft vein by flushing with arterial blood, a significantly lower platelet aggregability was seen in comparison with the systemic circulation before reperfusion in the control group, a difference that was not found when PGE1 infusion was given intraoperatively. However, blood product requirements during OLT were comparable in both groups. In conclusion, PGE1 therapy during OLT preserves platelet function and prevents the drop in platelet count observed in the control group after revascularization." ]

[ "8014707", "9462190", "19574255", "9347370", "9363656", "16163366", "7014814", "8951252", "10393602" ]

[ "Flow-synchronized ventilation of preterm infants with respiratory distress syndrome.", "Randomised trial of volume controlled versus time cycled, pressure limited ventilation in preterm infants with respiratory distress syndrome.", "Flow-cycled versus time-cycled sIPPV in preterm babies with RDS: a breath-to-breath randomised cross-over trial.", "Patient-initiated, pressure-regulated, volume-controlled ventilation compared with intermittent mandatory ventilation in neonates: a prospective, randomised study.", "Comparison of synchronized and conventional intermittent mandatory ventilation in neonates.", "Randomized, multicenter trial of conventional ventilation versus high-frequency oscillatory ventilation for the early management of respiratory failure in term or near-term infants in Colombia.", "Prospective clinical comparison of two methods for mechanical ventilation of neonates: rapid rate and short inspiratory time versus slow rate and long inspiratory time.", "The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.", "Randomized comparison of high-frequency ventilation with high-rate intermittent positive pressure ventilation in preterm infants with respiratory failure." ]

[ "Asynchrony of delivered and spontaneous breaths in mechanically ventilated infants may impair gas exchange and prolong the need for assisted ventilation. We conducted a randomized, controlled trial of a patient-triggered, flow-synchronized ventilator on 30 preterm infants with respiratory distress syndrome who weighed between 1100 and 1500 gm at birth. Entry criteria included radiographic evidence of respiratory distress syndrome and the need for mechanical ventilation and surfactant replacement therapy. Patients were assigned to either conventional time-cycled, pressure-limited ventilation or patient-triggered, flow-synchronized ventilation in an assist/control mode. Otherwise clinical management was identical. Time to extubation was the primary outcome measure. Patients treated with flow-synchronized ventilation were weaned more rapidly and had a significantly shorter mean time to extubation than those treated with time-cycled, pressure-limited ventilation, 119 versus 271 hours, p = 0.0152. In addition, there was no difference in the rate of complications between the two groups. There were, however, considerable reductions in patient charges of $4344 per patient in the flow-synchronized ventilation group.", "Fifty preterm infants weighing 1200 g or more with clinical and radiographic evidence of respiratory distress syndrome, requiring both mechanical ventilation and exogenous surfactant replacement, were randomly allocated to receive either volume controlled ventilation or time cycled, pressure limited ventilation. Tidal volume delivery in each group was deliberately controlled at 5-8 ml/kg so that the only difference between the two groups was the ventilatory modality, the manner in which tidal volume was delivered. The rest of the ventilatory management and clinical care was done according to protocol. The two modes of ventilation were compared by determining the time required to achieve pre-determined success criteria, based on either the alveolar-arterial oxygen gradient or the mean airway pressure as a standard against which the speed of weaning could be objectively assessed. Infants randomised to volume controlled ventilation met success criteria sooner and had a shorter duration of mechanical ventilation. These babies also had a significantly lower incidence of intraventricular haemorrhages and abnormal periventricular echodensities on ultrasound scans. Volume controlled ventilation seems to be both safe and effective in this group of patients.", "Few data exist about patient-triggered ventilation techniques in neonatal critical care. Our aim was to compare pressure-limited synchronised intermittent positive pressure (or assist/control) ventilation (sIPPV) in the classical time-cycled (TC-sIPPV) mode against flow-cycled (FC-sIPPV) modality. In this latter, typical sIPPV full respiratory support is provided but both the initiation and the end of inflation are determined by the infant's spontaneous respiratory efforts by using airway flow changes.\n A third-level neonatal intensive care unit.\n Ten preterm babies (<32 weeks' gestation) were randomised to receive 1 h FC-sIPPV followed by 1 h TC-sIPPV or the inverse shift, according to a computer-created randomisation table. Eligible babies had hyaline membrane disease and received 200 mg/kg surfactant at least 6 h before the study period. Respiratory mechanics, ventilatory and vital parameter data were registered real time.\n FC-sIPPV resulted in lower-rate volume ratio, pressure x rate product, mean airway pressure and heart rate; tidal volume and oxygen saturation were higher (all p<0.001). Spontaneous inspiratory time was lower than usually set by the physician and it was directly correlated to birth weight (rho = 0.5, p = 0.001) and gestational age (rho = 0.32, p = 0.001). No differences were noticed in the mechanics and blood gas and vital parameters during the two study phases.\n FC-sIPPV may safely result in a better patient ventilator synchrony. Inspiratory time usually set in neonatal critical care is higher than that decided by the baby during spontaneous effort. This should be considered when establishing time-cycled ventilation.", "To compare the effects of patient-initiated, pressure-regulated, volume-controlled ventilation (PRVC) with pressure-preset intermittent mandatory ventilation (IMV) in neonates with respiratory failure.\n Randomised, prospective study.\n Intensive care unit (14 beds) in a 300-bed paediatric teaching hospital.\n 60 neonates with respiratory distress syndrome (RDS) or congenital pneumonia, weighing < 2500 g and requiring mechanical ventilation.\n Ventilatory support until extubation via either IMV (n = 30) or PRVC (n = 27). In PRVC, the tidal volume (VT) was preset and pressure-controlled breaths delivered with peak inspiratory pressure values adapted to achieve the preset VT.\n Main outcome measures were duration of ventilation and incidence of bronchopulmonary dysplasia (BPD). Pulmonary air leaks and intraventricular haemorrhage (IVH) were considered major adverse effects. Demographic data, ventilation parameters and arterial/alveolar oxygen tension ratio were similar at randomisation. Duration of ventilation and incidence of BPD were not decreased by the use of PRVC. Air leaks occurred in 3 neonates in the PRVC group and in 7 babies treated with IMV (NS). The incidence of IVH grade > II was lower in babies treated with PRVC (p < 0.05). In a subgroup of neonates weighing < 1000 g, the duration of ventilation and incidence of hypotension were reduced in the PRVC group (p < 0.05).\n Patient-initiated, pressure-regulated, volume-controlled ventilation can be safely used in neonates and may contribute to a lower incidence of complications.", "Between October 1993 and April 1995, a total of 77 neonates requiring mechanical ventilation were enrolled in this study and were randomly divided into two groups. Group A consisted of 31 premature infants (mean birthweight 1.36 +/- 0.29 kg) with respiratory distress syndrome (RDS) and seven neonates (mean birthweight 3.2 +/- 0.5 kg) with meconium aspiration syndrome (MAS). Group B consisted of 31 premature infants (mean birthweight 1.31 +/- 0.3 kg) with RDS and eight neonates (mean birthweight 3.3 +/- 0.5 kg) with MAS. Infants in group A received synchronized intermittent mandatory ventilation (SIMV) and infants in group B received conventional intermittent mandatory ventilation (CIMV) therapy. In premature infants with RDS, our data showed: (i) the duration of ventilation was significantly shorter (P < 0.05) in the synchronized group (156 +/- 122 h) compared to the conventional group (242 +/- 175 h); (ii) significantly fewer (P < 0.05) patients required reintubation in the synchronized group than in the conventional group (three vs 11 patients); (iii) incidence of severe intraventricular hemorrhage (grades 3 and 4) was significantly lower (P < 0.05) in the synchronized group compared to the conventional group (one vs seven patients); (iv) incidence of bronchopulmonary dysplasia was significantly lower (P < 0.05) in the synchronized group than in the control group (one vs seven patients). In neonates with MAS, our data showed no significant difference (P < 0.05) on duration of ventilation, incidence of reintubation, incidence of pneumothorax or mortality rate between synchronized and control groups.", "To determine the efficacy and safety of high-frequency oscillatory ventilation (HFOV) compared to conventional ventilation (CV) for the treatment of respiratory failure in term and near-term infants in Colombia.\n Eligible infants with moderate to severe respiratory failure were randomized to early treatment with CV or HFOV. Ventilator management and general patient care were standardized. The main outcome was neonatal death or pulmonary air leak.\n A total of 119 infants were enrolled (55 in the HFOV group; 64 in the CV group) during the study period. Six infants in the HFOV group (11%) and two infants in the CV group (3%) developed the primary outcome (RR: 3.6, 95% CI: 0.8-16.9). Five infants in the HFOV group (9%) and one infant in the CV (2%) died before 28 days of life (RR: 5.9 CI: 0.7-48.2). Secondary outcomes were similar between groups.\n HFOV may not be superior to CV as an early treatment for respiratory failure in this age group. Standardization of ventilator management and general patient care may have a greater impact on the outcome in Colombia than mode of ventilation.\n Journal of Perinatology (2005) 25, 720-724. doi:10.1038/sj.jp.7211386; published online 15 September 2005.", "A prospective comparison was made of the clinical courses of two groups of neonates ventilated according to different protocols: one group at rates of 20 to 40/minute with a one-second IT, and the other at a rate of 60/minute and 0.5 second IT. Other ventilator settings were adjusted within protocol limits to maintain desired blood gas values. Mean starting and highest PIP were lower in the rapid rate group. The results showed no difference in mortality, failure to remain within protocol limits, time requiring respiratory treatment or FiO2 more than 0.6, and incidence of PDA or chronic lung disease. There was a difference (P = 0.011) in number of infants developing pneumothoraces (14% in the rapid group vs 35% in the slow group). Rapid rate ventilation can be used to decrease the incidence of pneumothorax, reserving long IT and higher PIP for infants who cannot be oxygenated or ventilated without them.", "To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support.\n A prospective randomized clinical trial.\n Three community-based level III neonatal intensive care units.\n A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50.\n Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit.\n No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants.\n When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.", "In a randomized, controlled, multicenter trial, we tested the hypothesis that high-frequency ventilation (HFV) with a high lung volume strategy results in fewer treatment failures than intermittent positive pressure ventilation (IPPV) with high rates and low peak inspiratory pressures.\n Infants with a gestational age between >/=24 weeks and <30 weeks, requiring mechanical ventilation within 6 hours of birth, were randomly assigned to receive either IPPV or HFV until 240 hours after randomization, extubation, or meeting treatment failure criteria. Treatment failure, the primary end point, was determined when air leaks, an oxygenation index >35 to 45 (depending on gestational age), death, or chronic lung disease occurred. Chronic lung disease was defined as persistent requirement of mechanical ventilation, continuous positive airway pressure, or supplemental oxygen at a postmenstrual age of 36 weeks. Secondary end points included the incidence of intracranial hemorrhage.\n The third scheduled interim analysis led to termination of the trial after recruitment of 284 infants. Treatment failure criteria were met by 46% of infants receiving IPPV and 54% of infants receiving HFV (1-tailed primary hypothesis, P =.92; 2-tailed chi2 test, P =.15). Air leaks occurred in 31% and 42% (P =.042), CLD in 23% and 25%, and grade 3-4 intracranial hemorrhage in 13% and 14% of IPPV-treated and HFV-treated patients, respectively. The mortality rate before discharge was 10% in both groups.\n HFV with a high lung volume strategy did not cause less lung injury in preterm infants than IPPV with a high rate and low peak inspiratory pressures." ]

[ "16962532", "18271883", "9609272", "12623472", "12842060", "19187377", "18506347", "12103284", "20680312" ]

[ "A randomized comparison of suturing techniques for episiotomy and laceration repair after spontaneous vaginal birth.", "Postpartum perineal repair performed by midwives: a randomised trial comparing two suture techniques leaving the skin unsutured.", "The Ipswich Childbirth Study: 1. A randomised evaluation of two stage postpartum perineal repair leaving the skin unsutured.", "A multicentre evaluation of the two-layered repair of postpartum perineal trauma.", "Does perineal suturing make a difference? The SUNS trial.", "Continuous versus interrupted sutures for repair of episiotomy or second-degree perineal tears: a randomised controlled trial.", "Randomized controlled clinical trial on two perineal trauma suture techniques in normal delivery.", "Continuous versus interrupted perineal repair with standard or rapidly absorbed sutures after spontaneous vaginal birth: a randomised controlled trial.", "Continuous versus interrupted episiotomy repair with monofilament or multifilament absorbed suture materials: a randomised controlled trial." ]

[ "To compare the continuous knotless technique of perineal repair with the interrupted method after spontaneous vaginal birth\n A randomized controlled trial.\n Canadian Task Force Classification I.\n This study was undertaken in a university hospital with more than 2200 deliveries per year. The static population of this district includes a wide range of socioeconomic classes and is predominately white.\n From May 1 to November 19, 2003, 214 primiparous women with a second-degree perineal tear or episiotomy were randomly allocated to either the continuous knotless technique (CKT; n=107) or the interrupted technique (IT; n=107) suturing method.\n The interrupted technique (IT) involves placing 3 layers of sutures whereas the continuous knotless technique (CKT) involves reapproximating vaginal trauma, perineal muscles, and skin with a loose, continuous, nonlocking technique.\n The primary outcomes of the study were perineal pain (evaluated by visual analogue scale) at 48 hours and day 10 and dyspareunia 3 months after delivery. Secondary outcomes included suture removal, wound dehiscence, analgesia use up to 48 hours, and satisfaction with repair established at 3 and 12 months after childbirth. At day 10, 19 women had dropped out of the study. Significantly fewer women reported pain at 10 days with the CKT than with the IT (32.3% vs 60.4%; p<.001). Analgesia use up to 48 hours postpartum was less in the CKT group than in the IT group (33.6% vs 54.2%; p<.05). No difference was found in superficial dyspareunia at 3 months for the CKT versus the IT group.\n The use of a continuous knotless technique for perineal repair is associated with less short-term pain than techniques with interrupted sutures.", "To compare a continuous suture technique with interrupted stitches using inverted knots for postpartum perineal repair of second-degree lacerations and episiotomies.\n A double-blind randomised controlled trial.\n A Danish university hospital with more than 4800 deliveries annually.\n A total of 400 healthy primiparous women with a vaginal delivery at term. METHOD Randomisation was computer-controlled. Structured interviews and systematic assessment of perineal healing were performed by research midwives blinded to treatment allocation at 24-48 hours, 10 days and 6 months postpartum. Pain was evaluated using a visual analogue scale and the McGill Pain Questionnaire. Wound healing was evaluated using the REEDA scale and by assessment of gaping wounds >0.5 cm. Analysis complied with the intention-to-treat principle.\n The primary outcome was perineal pain 10 days after delivery. Secondary outcomes were wound healing, patient satisfaction, dyspareunia, need for resuturing, time elapsed during repair and amount of suture material used.\n A total of 400 women were randomised; 5 women withdrew their consent, leaving 395 for follow up. The follow-up rate was 98% for all assessments after delivery. No difference was seen in perineal pain 10 days after delivery. No difference was seen in wound healing, patient satisfaction, dyspareunia or need for resuturing. The continuous suture technique was significantly faster (15 versus 17 minutes, P = 0.03) and less suture material was used (one versus two packets, P < 0.01).\n Interrupted, inverted stitches for perineal repair leaving the skin unsutured appear to be equivalent to the continuous suture technique in relation to perineal pain, wound healing, patient satisfaction, dyspareunia and need for resuturing. The continuous technique, however, is faster and requires less suture material, thus leaving it the more cost-effective of the two techniques evaluated.", "To evaluate a policy of two stage postpartum perineal repair leaving the skin unsutured.\n A stratified randomised controlled trial using a 2 x 2 factorial design.\n The maternity unit at Ipswich Hospital NHS Trust, a district general hospital, between 1992 and 1994.\n 1780 women requiring surgical repair of episiotomy or first or second degree tear following a spontaneous or simple instrumental delivery.\n A policy of two-stage perineal repair leaving skin unsutured was compared with a policy of three stage repair including skin closure with interrupted or subcuticular sutures. Both groups were assessed by a research midwife, blind to the allocation, completing questionnaires at 24 to 48 hours and 10 days postpartum, and by self-completed questionnaires at three months after birth.\n 1. 24 to 48 hours postpartum: perineal pain; healing; 2. 10 days postpartum: perineal pain, healing and removal of sutures; 3. three months postpartum: perineal pain, removal of sutures, resuturing, dyspareunia, and failure to resume pain-free intercourse.\n Completed questionnaires were returned for 99% of women at both 24 to 48 hours and ten days and by 93% of women three months postpartum. No differences were detected in perineal pain at 24 to 48 hours (62% vs 64%; RR 0.96, 95% CI 0.90-1.03; 2P = 0.3) and 10 days (25% vs 28%; RR 0.90, 95% CI 0.77-1.06; 2P = 0.2). Significantly fewer women allocated to two-stage repair reported tight stitches at ten days (14% vs 18%; RR 0.77, 95% CI 0.62-0.96, 2P = 0.02); similar numbers of repairs were judged to be breaking down (five compared with seven women). At three months postpartum fewer women allocated to the two-stage repair reported perineal pain and more had resumed pain-free intercourse. Amongst women who had resumed intercourse there was a significant difference in dyspareunia (15% vs 19%; RR 0.80, 95% CI 0.65-0.99; 2P = 0.04). Significantly fewer women in the two-stage repair group (7% vs 12%; RR 0.61, 95% CI 0.45-0.83; 2P = < 0.01) reported removal of suture material. Four women in the two-stage repair group had required resuturing, compared with nine allocated to the three-stage repair.\n Two-stage repair of perineal trauma leaving the skin unsutured appears to reduce pain and dyspareunia three months postpartum. There are no apparent disadvantages, in particular no evidence of an increased risk of breakdown of the repair and resuturing.", "We set out to compare a policy of two-layered postpartum perineal repair leaving the skin unsutured with a policy of three-layered repair, which involved skin closure. Parturients who sustained a second-degree tear or an episiotomy in four Nigerian centers were randomised to have either a two-layered repair (417 women) or a three-layered repair (406 women). Fewer women in the two-layered group reported perineal pain at 48 hours (57% vs. 65%, relative risk [RR] 0.87, 95% confidence interval [CI] 0.78-0.97) and 14 days postpartum (22% vs. 28%, RR 0.77, CI 0.61-0.98). The two-layered repair was also associated with reduced risk of suture removal (6% vs. 10%, RR 0.62, CI 0.39-0.99), and less superficial dyspareunia at 3 months (6% vs. 12%, RR 0.52, CI 0.33-0.81). The rates of wound healing were similar between the two groups. Leaving the skin unsutured during postpartum perineal repair reduces perineal pain and dyspareunia.", "To examine differences in outcome between primiparous women who do and who do not have suturing to first or second degree perineal lacerations sustained during spontaneous vaginal births after 37 weeks of gestation.\n Parallel group randomised controlled trial.\n Bellshill Maternity Hospital, Lanarkshire, and St John's Hospital, Livingston.\n Primigravidae with perineal lacerations following spontaneous birth.\n One thousand and three hundred fourteen women were recruited to the trial antenatally from whom 74 were randomised either to be sutured or not sutured immediately after giving birth. Randomisation was stratified by degree of tear.\n Using standardised measures, perineal pain and healing were measured at 1 and 10 days and 6 weeks postpartum. In addition, postnatal depression was assessed at 10 days and 6 weeks postpartum.\n Findings indicated that there were no significant differences between the groups with regard to pain or depression but there were differences with regard to healing. At six weeks, there remained a significant difference in wound closure between the groups, with women who had not been sutured having poorer wound approximation.\n While acknowledging the small sample size, the results are nonetheless important, showing persistent evidence of poorer wound approximation in those women who had not been sutured. Practitioners need to review the present practices of not suturing perineal lacerations until research examining the longer term implications is undertaken.", "To evaluate the repair techniques of continuous and interrupted methods for episiotomy or perineal tears.\n A randomised controlled trial.\n The Hospital Universitario Principe de Asturias, a state hospital belonging to the community of Madrid.\n Four hundred forty-five women who had undergone vaginal deliveries with episiotomies or second-grade tearing of the perineum between September 2005 and July 2007.\n One group was repaired with continuous, nonlocking sutures involving the vagina, perineum, and subcutaneous tissues. The other group had continuous, locking sutures of the vagina, interrupted sutures in the perineal muscles, and interrupted transcutaneous sutures. The threads used for stitching were identical in both groups.\n The participants were questioned regarding the sensation of pain and the use of painkillers on the second and the tenth days, and 3 months postpartum.\n When comparing the group with continuous suture to the group with interrupted sutures, the differences included less repair time (1 minute; P= 0.017) and less suture material used (relative risk [RR], 3.2, 95% CI: 2.6-4.0). The comparison of pain on the second and tenth days, and 3 months postpartum were not statistically different between the two techniques (RR, 1.08, 95% CI: 0.74-1.57; RR, 0.96, 95% CI: 0.59-1.55; and RR, 0.68, 95% CI: 0.19-2.46, respectively).\n Although we did not demonstrate that one technique was better than the other in the incidence of pain in the short or long term, we showed that episiotomy and perineal tear repairs with continuous suturing were quicker and used less suture material without an increase in complication than interrupted suturing.", "The aim was to compare healing and perineal pain with the use of continuous and interrupted suture techniques in women after normal delivery. A randomized controlled trial was carried out at a hospital birth center in Itapecirica da Serra, Sao Paulo, Brazil. A total of 61 women participated with episiotomy or second degree perineal tear, allocated in two groups according to the continuous (n=31) or interrupted (n=30) suture techniques. The main outcomes evaluated were edema, ecchymosis, hyperemia, secretion, dehiscence, fibrosis, frequency and degree of pain (evaluated by numerical scale from 1 to 10). Data were collected during hospitalization and after discharge (four and 41 days after birth). Healing occurred by first intention in 100% of cases in both suture techniques. There were no statistically significant differences for the occurrence of morbidities, except for perineal pain due to palpation at four days after delivery, which was more frequent among women with interrupted suture.", "Trauma to the perineum is a serious and frequent problem after childbirth, with about 350000 women each year in the UK needing sutures for perineal injury after spontaneous vaginal delivery, and many millions more worldwide. We compared the continuous technique of perineal repair with the interrupted method, and the more rapidly absorbed polyglactin 910 suture material with the standard polyglactin 910 material.\n 1542 women who had a spontaneous vaginal delivery with a second-degree perineal tear or episiotomy were randomly allocated to either the continuous (n=771) or interrupted (771) suturing method, and to either the more rapidly absorbed polyglactin 910 suture material (772) or standard polyglactin 910 material (770). Primary outcomes were pain 10 days after delivery and superficial dyspareunia 3 months postpartum. Analysis was by intention to treat.\n At day 10, three women had dropped out of the study. Significantly fewer women reported pain at 10 days with the continuous technique than with the interrupted method (204/770 [26.5%] vs 338/769 [44.0%], odds ratio 0.47, 95% CI 0.38-0.58, p<0.0001). Occurrence of pain did not differ significantly between groups assigned the more rapidly absorbed material or standard material (256/769 [33.3%] vs 286/770 [37.1%], 0.84, 0.68-1.04, p=0.10). Women reported no difference in superficial dyspareunia at 3 months for the continuous vs the interrupted method (98/581 [16.9%] vs 102/593 [17.2%], 0.98, 0.72-1.33, p=0.88) or the more rapidly absorbed versus standard material (105/586 [17.9%] vs 95/588 [16.2%], 1.13, 0.84-1.54, p=0.42). Suture removal was done less with the more rapidly absorbed material than with standard suture material (22/769 [3%] vs 98/770 [13%], p<0.0001), and with the continuous versus interrupted method (24/770 [3%] vs 96/769 [12%], p<0.0001).\n A simple and widely practicable continuous repair technique can prevent one woman in six from having pain at 10 days. Also, the more rapidly absorbed polyglactin 910 material obviates need for suture removal up to 3 months postpartum for one in ten women sutured.", "To compare different repair techniques and different suture materials for episiotomy.\n 160 women having vertex delivery with right-mediolateral episiotomy were randomly allocated to four groups. In the groups where continuos technique was performed, vaginal mucosa, perineal muscles and the skin were sutured continuously. In the groups of interrupted technique, vaginal mucosa was sutured with continuous sutures, then muscle layers and skin were closed by interrupted sutures. Two different types of synthetic absorbed suture material were used: monofilament type is in form of polyglycolide-co-caprolactone and multifilament one is polyglactin 910-Rapide. Perineal pain during different activities on the first and tenth day postpartum and also during sexual intercourse 6 weeks after the delivery was questioned by visual analogous scale (VAS). Furthermore, repair time, amount of suture and episiotomy complications were investigated in each groups.\n On the first day after delivery, the perineal pain scores, the repair time, the amount of suture were statistically less in the continuous technique groups. The differences between the pain at tenth day and during sexual intercourse 6 weeks after the delivery were statistically same.\n The continuous suturing techniques for episiotomy closure, compared to interrupted methods, are associated with less short-term pain, are quicker and also need less suture material." ]

[ "10207925", "9708751", "9105740", "12763331", "11985388", "3897499", "6440704", "12740260", "1595097" ]

[ "Acetazolamide and furosemide for posthemorrhagic hydrocephalus of the newborn.", "International randomised controlled trial of acetazolamide and furosemide in posthaemorrhagic ventricular dilatation in infancy. International PHVD Drug Trial Group.", "Failure of fibrinolytic endoventricular treatment to prevent neonatal post-haemorrhagic hydrocephalus. A case-control trial.", "Intraventricular streptokinase for the treatment of posthaemorrhagic hydrocephalus of preterm.", "Efficacy and tolerability of acetazolamide in migraine prophylaxis: a randomised placebo-controlled trial.", "Serial lumbar punctures in prevention of post-hemorrhagic hydrocephalus in preterm infants.", "The University of Toronto head injury treatment study: a prospective, randomized comparison of pentobarbital and mannitol.", "Comparison of acetazolamide and medroxyprogesterone as respiratory stimulants in hypercapnic patients with COPD.", "Evaluation of vasomotor reactivity by transcranial Doppler and acetazolamide test before and after extracranial-intracranial bypass in patients with internal carotid artery occlusion." ]

[ "The authors evaluated the efficacy of acetazolamide (ACZ) and furosemide (FUR) in avoiding ventricular shunting procedures in preterm infants with posthemorrhagic hydrocephalus (PHH) and increased intracranial pressure (ICP). Preterm infants were screened for PHH (defined as ventriculomegaly [VM] and increased ICP measured with the Ladd fiberoptic monitor). PHH infants were randomized to ACZ and FUR treatment or serial lumbar puncture (LP) and monitored until not receiving medications or having undergone shunting. Of 69 infants with IVH screened for the study, 39 never developed VM, 14 developed VM, without increased ICP, and 16 developed PHH. Ten PHH infants were randomized to ACZ and FUR treatment and six to serial LP. Nine (90%) of the 10 infants assigned to the ACZ and FUR group avoided shunting. Nephrocalcinosis developed in a significant proportion of treated infants. Three (50%) of the six LP group infants did not require shunting procedures (P = 0.118). The authors conclude that ACZ and FUR therapy is useful in the treatment of preterm infants with PHH. Because a significant number of infants treated with both ACZ and FUR developed nephrocalcinosis, close monitoring for increased calcium excretion in the urine, or use of ACZ without FUR, is advised.", "Furosemide and acetazolamide are widely used in the treatment of posthaemorrhagic ventricular dilatation (PHVD) in the hope of avoiding the need for surgical management, but this approach has not been evaluated in a controlled trial. This multicentre randomised controlled trial tested the hypothesis that these drugs would reduce the rate of shunt placement and increase disability-free survival at 1 year of age.\n Between 1992 and 1996, 177 infants aged less than 3 months past term, and with ventricular width more than 4 mm above 97th centile after intraventricular haemorrhage, were randomly assigned standard therapy alone or standard therapy plus treatment with acetazolamide (100 mg/kg daily) and furosemide (1 mg/kg daily). A minimisation algorithm ensured balance between groups with respect to both referral centre and the presence of a cerebral parenchymal lesion on cerebral ultrasonography at enrolment. The trial was stopped in September, 1996, because the data showed a clear advantage with standard therapy.\n We report outcomes for 151 infants whose expected date of delivery was before the end of 1995, with complete information at 1 year for 129 infants. The median gestational age was 28 weeks, mean birthweight 1299 g, and mean postnatal age at enrolment 25 days. 44% had a parenchymal lesion at randomisation. Death or shunt placement occurred in 49 of 75 infants allocated drugs plus standard therapy, compared with 35 of 76 allocated to standard therapy alone. The relative risk was 1.42 (95% CI 1.06-1.90; p=0.026), which is equivalent to one extra death or shunt placement for every five infants allocated drug therapy. 84% (52/62) of infants assigned drug therapy had died or were disabled or impaired at 1 year, compared with 60% (40/67) of those assigned standard therapy (relative risk 1.40 [1.12-1.76]; p=0.012).\n These preliminary results suggest that the use of acetazolamide and furosemide in preterm infants with PHVD is associated with a higher rate of shunt placement and increased neurological morbidity, and so cannot be recommended.", "Post-haemorrhagic hydrocephalus is assumed to result from obstruction of the cerebrospinal fluid (CSF) pathways by blood clots and subsequent chronic infiltration with collagen. The aim of this work was to evaluate the possibility of preventing permanent shunt dependence by enhancing the endoventricular fibrinolysis by means of an endoventricular streptokinase infusion in babies affected by posthaemorrhagic ventricular dilation. A case-control trial was carried out in 12 neonates affected by intraventricular haemorrhage and subsequent progressive ventriculomegaly. Six of them were treated with 20,000 U/day of streptokinase infused over 96 h through a percutaneous ventricular catheter. Our results show that the percentage of shunted babies was identical in treated and control patients despite the enhancement of endoventricular fibrinolysis obtained in all treated patients. On the basis of our results we do not recommend intraventricular streptokinase infusion for routine use in post-haemorrhagic ventricular dilatation.", "Posthaemorrhagic hydrocephalus following intraventricular haemorrhage is still one of the most serious complications of premature birth. Small premature babies are not suitable for shunt surgery because of high cerebrospinal fluid protein and risk of obstruction. For this reason there is a great need for alternative approaches for treatment of posthaemorrhagic hydrocephalus. The objective of this study was to investigate if intraventricular streptokinase treatment reduces the need for ventriculoperitoneal shunt in posthaemorrhagic hydrocephalus. A case-control trial was carried out in 12 premature babies with posthaemorrhagic hydrocephalus. Six of them were treated with intraventricular streptokinase and 6 premature babies were in the control group. While 5 babies in the study group needed ventriculoperitoneal shunt, 3 of the control patients needed shunt surgery. There were no rebleeding, ventriculitis or meningitis in either groups. In conclusion on the basis of our results we do not recommend routine use of intraventricular streptokinase in posthaemorrhagic hydrocephalus.", "Familial hemiplegic migraine and episodic ataxia type 2 (EA2) are allelic disorders with distinct types of mutations in the CACNA1A gene. EA2 attacks are remarkably sensitive to acetazolamide, a carbonic anhydrase inhibitor. The effectiveness of acetazolamide in migraine prophylaxis is unknown.\n To evaluate the efficacy and the tolerability of acetazolamide in migraine prophylaxis.\n We compared daily oral 500 mg acetazolamide and placebo in patients with migraine in a multicentre, double-blind, randomised trial of 12 weeks duration after a run-in period of 4 weeks without treatment. Frequency of attacks at the last trial period of 4 weeks was the primary efficacy criterion. Secondary efficacy criteria were the frequency of attacks per 4 weeks, the severity and duration of attacks, the number of hours with migraine as well as the number of responders with more than 50% reduction in attack frequency.\n 53 patients had been enrolled when the study was prematurely stopped because of a high number of withdrawals (34%), primarily linked to acetazolamide related side effects. Considering the primary and secondary efficacy criteria, among the 53 included patients (27 in the placebo group and 26 in the acetazolamide group), no difference between the 2 study groups could be demonstrated. The most frequent adverse events related to acetazolamide were paresthesias and asthenia.\n In this trial, migraine sufferers poorly tolerated acetazolamide given in an oral dose of 500 mg daily. No obvious prophylactic beneficial effect of acetazolamide appeared on migraine attacks.", "We studied 47 infants with either grade 3 or grade 4 intraventricular hemorrhage, to assess the efficacy of intermittent lumbar punctures in the prevention of post-hemorrhagic hydrocephalus in a prospective controlled trial. The control group received supportive care only, whereas the treatment group additionally underwent intermittent spinal taps. The spinal taps were started at postnatal age 11 +/- 5 days and continued for 20 +/- 16 days, with the removal of 67 +/- 101 ml cerebrospinal fluid using 16 +/- 12 taps. The two groups were comparable with regard to birth weight, gestational age, race, sex, Apgar score, and severity of hemorrhage. Three infants in the control group died, compared with two infants in the study group. Nine infants in the control group and 10 infants in the study group developed hydrocephalus requiring a ventriculoperitoneal shunt or a ventricular catheter reservoir. These differences in the outcome in the two groups are not statistically significant. We conclude that serial lumbar punctures were unsuccessful in prevention of hydrocephalus in this group of preterm infants with intraventricular hemorrhage.", "Fifty-nine patients were treated in a prospective, randomized comparison of pentobarbital and mannitol for the control of intracranial hypertension resulting from head injury. Patients with elevated intracranial pressure (ICP) after evacuation of intracranial hematomas were randomized to one of two treatment groups; mannitol initially or pentobarbital initially, followed by the second drug as required by further elevation of ICP. Similarly, patients with raised ICP but without hematomas requiring evacuation were randomly assigned to two treatment groups in an identical paradigm. Those with ICP elevation and no hematoma treated with pentobarbital as initial therapy had a 77% mortality compared to a 41% mortality for those with mannitol as initial treatment. Patients with evacuated hematomas had mortalities of 40% and 43% (no significant difference) for pentobarbital and mannitol respectively. In both no-hematoma and hematoma streams pentobarbital was less effective than mannitol for control of raised ICP. Multivariable statistical analysis indicates that pentobarbital coma is not better than mannitol for the treatment of intracranial hypertension and may be harmful in no-hematoma patients with intracranial hypertension after head injury.", "Acetazolamide and medroxyprogesterone acetate (MPA) are two respiratory stimulants that can be used in patients with stable hypercapnic COPD.\n The effects of acetazolamide, 250 mg bid, and MPA, 30 mg bid, on daytime and nighttime blood gas values and the influences on the hypercapnic and hypoxic ventilatory and mouth occlusion pressure (P(0.1)) at 100 ms response were studied in a crossover design in 12 hypercapnic patients with stable COPD (FEV(1), 33 +/- 4% predicted [mean +/- SEM]).\n Daytime PaCO(2) decreased from 47.3 +/- 0.8 mm Hg (placebo) to 42.0 +/- 1.5 mm Hg during acetazolamide treatment (p < 0.05) and to 42.8 +/- 1.5 mm Hg during MPA treatment (p < 0.05). Daytime PaO(2) improved with acetazolamide from 65.2 +/- 2.3 to 75.0 +/- 3.0 mm Hg (p < 0.05), whereas no significant changes were seen with MPA. Mean nocturnal end-tidal carbon dioxide tension decreased with both treatments, from 42.0 +/- 2.3 to 35.3 +/- 2.3 mm Hg with acetazolamide (p < 0.05) and to 34.5 +/- 0.8 mm Hg with MPA (p < 0.05). The percentage of time that the nocturnal arterial oxygen saturation was < 90% was reduced significantly with acetazolamide, from 34.9 +/- 10.7% to 16.3 +/- 7.5% (p < 0.05). Mean nocturnal saturation did not change with MPA. Resting minute ventilation increased significantly only with MPA from 9.6 +/- 0.7 to 10.8 +/- 0.8 L/min (p < 0.05). The slope of the hypercapnic ventilatory response did not change during acetazolamide and MPA therapy. The hypoxic ventilatory response increased from - 0.2 +/- 0.05 to - 0.4 +/- 0.1 L/min/% during acetazolamide (p < 0.05) and to - 0.3 +/- 0.1 L/min/% during MPA (p < 0.05). The hypoxic P(0.1) response improved with acetazolamide treatment from - 0.05 +/- 0.008 to - 0.15 +/- 0.02 mm Hg/% (p < 0.05).\n This study shows that acetazolamide and MPA both have favorable effects on daytime and nighttime blood gas parameters in ventilatory-limited patients with stable COPD. However, the use of acetazolamide is preferred because of its extra effect on nocturnal saturation.", "The aim of this trial was to evaluate the effectiveness of extracranial-intracranial bypass with respect to vasomotor reactivity in patients with internal carotid artery occlusions and absent vasomotor reactivity, comparing them with a control group treated conservatively.\n To test vasomotor reactivity in 104 patients with unilateral occlusion of the internal carotid artery, we measured blood flow velocity in the middle cerebral artery by transcranial Doppler sonography both at rest and after injection of acetazolamide. Among the 39 patients who failed to show increased mean blood flow velocity after the acetazolamide test distal to an occluded internal carotid artery by greater than or equal to 10%, 14 subjects subsequently underwent extracranial-intracranial bypass surgery (group A) and 14 age- and sex-matched subjects in whom no such procedure was done composed the control group (group B). Follow-up examinations were performed 3-6 months postoperatively and in the control group 3-6 months after initial examination.\n Baseline values of the mean blood flow velocity at rest on the affected side were reduced in both groups compared with the contralateral healthy side (group A, 46.0 +/- 15.1 cm/sec; group B, 48.1 +/- 16.7 cm/sec) and revealed only a marginal increase after acetazolamide. The contralateral side showed a normal blood flow velocity at rest and an adequate response to acetazolamide in both groups. On the follow-up examination group A demonstrated a normalized vasodilatory capacity. Blood flow velocity increased significantly after acetazolamide from 41.9 +/- 13.1 cm/sec to 53.5 +/- 16.0 cm/sec (p less than 0.002). In group B, the compromised vasomotor reactivity remained unchanged.\n Our results demonstrate that transcranial Doppler sonography together with the acetazolamide test can identify subjects with reduced vasomotor reactivity distal to an occluded internal carotid artery, who may improve hemodynamically by an extracranial-intracranial bypass." ]

[ "6384785", "12186604", "12133187", "9559600", "3306374", "18184957", "786190", "16625008", "20103758" ]

[ "The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study.", "Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.", "Physiological-dose steroid therapy in sepsis [ISRCTN36253388].", "Reversal of late septic shock with supraphysiologic doses of hydrocortisone.", "A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock.", "Hydrocortisone therapy for patients with septic shock.", "Steroids in the treatment of clinical septic shock.", "Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.", "Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial." ]

[ "To determine whether corticosteroids are efficacious in severe septic shock, we conducted a prospective study of 59 patients randomly assigned to a methylprednisolone, dexamethasone, or control group. Patients were treated 17.5 +/- 5.4 hours (mean +/- S.E.M.) after the onset of shock, and 55 patients required vasopressor agents. Early in the hospital course, reversal of shock was more likely in patients who received corticosteroids than in those who did not. Four (19 per cent) of 21 methylprednisolone-treated, 7 (32 per cent) of 22 dexamethasone-treated, and none of 16 control patients had reversal of shock 24 hours after drug administration (corticosteroid groups vs. control group, P less than 0.05). Patients treated with corticosteroids within four hours after the onset of shock had a higher incidence of shock reversal (P less than 0.05). At 133 hours after drug administration, 17 (40 per cent) of 43 corticosteroid-treated patients had died, and 11 (69 per cent) of 16 control patients had died (P less than 0.05). However, these differences in reversal of shock and survival disappeared later in the course. Overall, 16 (76 per cent) of 21 patients receiving methylprednisolone, 17 (77 per cent) of 22 patients receiving dexamethasone, and 11 (69 per cent) of 16 controls in the hospital died. We conclude that corticosteroids do not improve the overall survival of patients with severe, late septic shock but may be helpful early in the course and in certain subgroups of patients.", "Septic shock may be associated with relative adrenal insufficiency. Thus, a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock.\n To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency.\n Placebo-controlled, randomized, double-blind, parallel-group trial performed in 19 intensive care units in France from October 9, 1995, to February 23, 1999.\n Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test.\n Patients were randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7 days.\n Twenty-eight-day survival distribution in patients with relative adrenal insufficiency (nonresponders to the corticotropin test).\n One patient from the corticosteroid group was excluded from analyses because of consent withdrawal. There were 229 nonresponders to the corticotropin test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval, 1.29-2.84; P =.001). There was no significant difference between groups in responders. Adverse events rates were similar in the 2 groups.\n In our trial, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events.", "The aim of the study was to assess the prognostic importance of basal cortisol concentrations and cortisol response to corticotropin, and to determine the effects of physiological dose steroid therapy on mortality in patients with sepsis.\n Basal cortisol level and corticotropin stimulation test were performed within 24 hours in all patients. One group (20 patients) received standard therapy for sepsis and physiological-dose steroid therapy for 10 days; the other group (20 patients) received only standard therapy for sepsis. Basal cortisol level was measured on the 14th day in patients who recovered. The outcome of sepsis was compared.\n Only Sequential Organ Failure Assessment (SOFA) score was found related to mortality, independent from other factors in multivariate analysis. No significant difference was found between the changes in the percentage of SOFA scores of the steroid therapy group and the standard therapy group in survivors, nor between the groups in basal and peak cortisol levels, cortisol response to corticotropin test and mortality. The mortality rates among patients with occult adrenal insufficiencies were 40% in the steroid therapy group and 55.6% in the standard therapy group.\n There was a trend towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy. In the advancing process from sepsis to septic shock, adrenal insufficiency was not frequent as supposed. There was a trend (that did not reach significance) towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy.", "Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines. We examined the effect of hydrocortisone on shock reversal, hemodynamics, and survival in this particular setting.\n Prospective, randomized, double-blind, placebo-controlled study.\n Two intensive care units of a University hospital.\n Forty-one patients with septic shock requiring catecholamine for >48 hrs.\n Patients were randomly assigned either hydrocortisone (100 mg i.v. three times daily for 5 days) or matching placebo.\n Reversal of shock was defined by a stable systolic arterial pressure (>90 mm Hg) for > or =24 hrs without catecholamine or fluid infusion. Of the 22 hydrocortisone-treated patients and 19 placebo-treated patients, 15 (68%) and 4 (21%) achieved 7-day shock reversal, respectively, a difference of 47% (95% confidence interval 17% to 77%; p = .007). Serial invasive hemodynamic measurements for 5 days did not show significant differences between both groups. At 28-day follow-up, reversal of shock was higher in the hydrocortisone group (p = .005). Crude 28-day mortality was 7 (32%) of 22 treated patients and 12 (63%) of 19 placebo patients, a difference of 31% (95% confidence interval 1% to 61%; p = .091). Shock reversal within 7 days after the onset of corticosteroid therapy was a very strong predictor of survival. There were no significant differences in outcome in responders and nonresponders to a short corticotropin test. The respective rates of gastrointestinal bleeding and secondary infections did not differ between both groups.\n Administration of modest doses of hydrocortisone in the setting of pressor-dependent septic shock for a mean of >96 hrs resulted in a significant improvement in hemodynamics and a beneficial effect on survival. These beneficial effects do not appear related to adrenocortical insufficiency.", "The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.", "Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin.\n In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test.\n Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock.\n Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. (ClinicalTrials.gov number, NCT00147004.)\n 2008 Massachusetts Medical Society", "A prospective (Part I) and a retrospective (Part II) study were used to determine the safety and efficacy of corticosteroids in the treatment of septic shock. In Part I, 172 consecutive patients in septic shock admitted over an 8-year period were treated with either steroid or saline: 43 received dexamethasone (DMP), 43 received methylprednisolone (MPS), and 86 received saline. The study was double-blind and randomized, and the three groups were compared for age, severity of shock, presence of underlying disease, and year of study. In the 86 saline-treated patients, the mortality rate was 38.4% (33/86); in the steroid-treated patients, it was 10.4% (9/86). With MPS the mortality rate was 11.6% (5/43), and with DMP it was 9.3% (4/43). Thus, overall mortality was significantly less in the steroid-treated group than in the control group. Further, there was no significant difference in mortality rate between the DMP- and the MPS-treated patients. In Part II, 328 patients were studied retrospectively. One-hundred sixty were treated without steroid, and 168 were treated with either DMP or MPS. Again, the two groups of patients were compared for severity of shock, underlying disease, age, and year of study. Mortality among patients treated without steroid was 42.5% (68/160) and among patients treated with steroid was 14% (24/168); there was no significant difference in mortality rate between DMP- and MPS-treated patients. In Parts I and II combined, complications occurred in 6% of steroid-treated patients with no significant difference between DMP- and MPS-treated groups.", "Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.\n We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications.\n At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.\n These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.).\n Copyright 2006 Massachusetts Medical Society.", "Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear.\n To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone.\n A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France.\n Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days.\n In-hospital mortality.\n Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50).\n Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock. The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality.\n clinicaltrials.gov Identifier: NCT00320099." ]

[ "11493843", "15770171", "14521638", "10828925", "14965404", "8066514", "18408345", "15507794", "21303529" ]

[ "A randomized controlled trial to prevent patient lift and transfer injuries of health care workers.", "Implementation of the Dutch low back pain guideline for general practitioners: a cluster randomized controlled trial.", "Randomized controlled trial of education and feedback for implementation of guidelines for acute low back pain.", "A controlled trial of an educational pamphlet to prevent disability after occupational low back injury.", "Implementation of RCGP guidelines for acute low back pain: a cluster randomised controlled trial.", "Intensive physical and psychosocial training program for patients with chronic low back pain. A controlled clinical trial.", "Effect of nursing assistance tools on preventing musculoskeletal pain among staff in schools for disabled children.", "Early intervention for the management of acute low back pain: a single-blind randomized controlled trial of biopsychosocial education, manual therapy, and exercise.", "A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain." ]

[ "Randomized controlled trial (RCT).\n To compare the effectiveness of training and equipment to reduce musculoskeletal injuries, increase comfort, and reduce physical demands on staff performing patient lifts and transfers at a large acute care hospital.\n Back injury to nursing staff during patient handling tasks is a major issue in health care. The value of mechanical assistive devices in reducing injuries to these workers is unclear.\n This three-armed RCT consisted of a \"control arm,\" a \"safe lifting\" arm, and a \"no strenuous lifting\" arm. A medical, surgical, and rehabilitation ward were each randomly assigned to each arm. Both intervention arms received intensive training in back care, patient assessment, and handling techniques. Hence, the \"safe lifting\" arm used improved patient handling techniques using manual equipment, whereas the \"no strenuous lifting\" arm aimed to eliminate manual patient handling through use of additional mechanical and other assistive equipment.\n Frequency of manual patient handling tasks was significantly decreased on the \"no strenuous lifting\" arm. Self-perceived work fatigue, back and shoulder pain, safety, and frequency and intensity of physical discomfort associated with patient handling tasks were improved on both intervention arms, but staff on the mechanical equipment arm showed greater improvements. Musculoskeletal injury rates were not significantly altered.\n The \"no strenuous lifting\" program, which combined training with assured availability of mechanical and other assistive patient handling equipment, most effectively improved comfort with patient handling, decreased staff fatigue, and decreased physical demands. The fact that injury rates were not statistically significantly reduced may reflect the less sensitive nature of this indicator compared with the subjective indicators.", "Cluster randomized controlled trial for a multifaceted implementation strategy.\n To assess the effectiveness of tailored interventions (multifaceted implementation strategy) to implement the Dutch low back pain guideline for general practitioners with regard to adherence to guideline recommendations.\n Guidelines for the management of low back pain in primary care have been developed in various countries, but little is known about the optimal implementation strategy. A multifaceted implementation strategy was developed to overcome identified barriers to the implementation of the Dutch low back pain guideline for general practitioners.\n General practitioners were randomized to an intervention or a control group. The general practitioners in the intervention group (n = 21) received tailored interventions consisting of the Dutch low back pain guideline for general practitioners, a 2-hour educational and clinical practice workshop; two scientific articles on low back pain management; the guideline for occupational physicians; a tool for patient education; and a tool for reaching agreement on low back care with physical, exercise, and manual therapists. The control group (n = 20) received no intervention. The participating general practitioners were asked to recruit consecutive patients with a new episode of low back pain as the main reason for consultation. General practitioners completed registration forms of each individual consultation with regard to the main outcome measures: advice and information, referral to other health-care providers, and prescription of medication.\n Forty-one of the 67 randomized general practitioners reported on a total of 616 consultations for 531 patients with nonspecific low back pain. The advice and explanation provided by the general practitioners, the prescription of paracetamol or nonsteroidal anti-inflammatory drugs, and prescription of pain medication on atime contingent or a pain contingent basis showed no statistically significant differences between the intervention and control groups. There were also no differences in overall referral rate. However, in follow-up consultations fewer patients were referred to a physical or exercise therapist by the general practitioners in the intervention group than in the control group.\n The multifaceted intervention strategy modestly improved implementation (for parts of the recommendations in) the Dutch low back pain guideline by general practitioners and produced small concomitant changes in patient management. The implementation strategy produced fewer referrals to therapists during follow-up consultations.", "The effect of clinical guidelines on resource utilization for complex conditions with substantial barriers to clinician behavior change has not been well studied. We report the impact of a multifaceted guideline implementation intervention on primary care clinician utilization of radiologic and specialty services for the care of acute low back pain.\n Physician groups were randomized to receive guideline education and individual feedback, supporting patient education materials, both, or neither. The impact on guideline adherence and resource utilization was evaluated during the 12-month period before and after implementation.\n Fourteen physician groups with 120 primary care physician and associate practitioners from 2 group model HMO practices.\n Guideline implementation utilized an education/audit/feedback model with local peer opinion leaders. The patient education component included written and videotaped materials on the care of low back pain.\n The clinician intervention was associated with an absolute increase in guideline-consistent behavior of 5.4% in the intervention group versus a decline of 2.7% in the control group (P =.04). The patient education intervention produced no significant change in guideline-consistent behavior, but was poorly adopted. Patient characteristics including duration of pain, prior history of low back pain, and number of visits during the illness episode were strong predictors of service utilization and guideline-consistent behavior.\n Implementation of an education and feedback-supported acute low back pain care guideline for primary care clinicians was associated with an increase in guideline-consistent behavior. Patient education materials did not enhance guideline effectiveness. Implementation barriers could limit the utility of this approach in usual care settings.", "Randomized controlled trial.\n To test the ability of an educational pamphlet to improve recovery in terms of pain, work status, and health care utilization after occupational low back injury.\n Low back pain and disability persist as occupational health problems of epidemic proportions. Because interventions based on biomechanical models have had limited impact, recent educational approaches to preventing back problems have stressed psychosocial recovery issues.\n A pamphlet was developed by compiling activity resumption, self-care, and attitudinal advice from recent publications. The pamphlet was sent at random to half of all consenting workers reporting back pain within 11 days of occupational injury between 7/96 and 6/97. Three and 6 months later, back pain, work status, health care use, and pamphlet impact outcomes were assessed through structured telephone interviews.\n Of the 726 eligible workers, 486 consented to participate. Consenters and nonconsenters and intervention and control groups were similar in initial demographic variables. The pamphlet had no statistically significant impact at the 0.05 significance level on pain severity or reduction, health care visits, or work absence. Of the 229 pamphlet recipients, 129 thought it had provided useful information, but only 25 thought it had helped them return to work more quickly.\n In this trial, a pamphlet stressing psychosocial recovery issues did not prevent or reduce postinjury pain, health care use, or work absence.", "The Royal College of General Practitioners (RCGP) has produced guidelines for the management of acute low back pain in primary care.\n To investigate the impact on patient management of an educational strategy to promote these guidelines among general practitioners (GPs).\n Group randomised controlled trial, using the health centre as the unit of randomisation.\n Primary care teams in north-west England.\n Twenty-four health centres were randomly allocated to an intervention or control arm. Practices in the intervention arm were offered outreach visits to promote national guidelines on acute low back pain, as well as access to fast-track physiotherapy and to a triage service for patients with persistent symptoms.\n Twenty-four centres were randomised. Two thousand, one hundred and eighty-seven eligible patients presented with acute low back pain during the study period: 1049 in the intervention group and 1138 in the control group. There were no significant differences between study groups in the proportion of patients who were referred for X-ray, issued with a sickness certificate, prescribed opioids or muscle relaxants, or who were referred to secondary care, but significantly more patients in the intervention group were referred to physiotherapy or the back pain unit (difference in proportion = 12.2%, 95% confidence interval [CI] = 2.8% to 21.6%).\n The management of patients presenting with low back pain to primary care was mostly unchanged by an outreach educational strategy to promote greater adherence to RCGP guidelines among GPs. An increase in referral to physiotherapy or educational programmes followed the provision of a triage service.", "The authors conducted a controlled clinical trial with 1-year follow-up to define the effectiveness of an intensive physical and psychosocial training program on patients with low back pain.\n The intervention group included 152 patients (mean age 40.5 yr, Million index 45.1/100), and the reference group included 141 patients (mean age 40.4 yr, Million-index 44.5/100).\n The progressive intervention program consisted of intensive physical training and psychosocial activation. The outcomes were physical and psychosocial measures, the pain and disability index (Million), sick leaves, and occupational handicap.\n The intervention was more efficient with respect to physical measures and pain and disability index. There were only mild or no differences in changes between the study groups in psychologic variables, sick leaves, or retirement.\n The intervention program could improve physical disability, but to improve occupational handicap, activities of the whole society (social legislation, labor market policy) are needed.", "Objective is to clarify whether nursing assistance tools (a mat with attached handles, a pair of trousers with knee pads and a waist holding belt) prevent musculoskeletal pain, such as low back pain and upper arm pain, and depression, and improve the burden on the lower back and upper arm among staff in schools for disabled children. This study design was a non-randomized intervention trial. The subjects were 41 staff in two schools for disabled children in Japan. Nursing assistance tools were used with the intervention group to help with their nursing activities. We investigated the one-month prevalence of low back pain and the degree of burden on the lower back using a questionnaire at the baseline and at the end point 4 to 6 months later. The prevalence of low back pain did not change significantly in either group. In the intervention group, the prevalence of upper arm pain decreased from 47.6% at the baseline to 23.8% at the end point (p=0.063). The percentage of participants with a high level of burden on the lower back from excretory nursing activity decreased from 57.1% at the baseline to 33.3% at the end point (p=0.063) in the intervention group. These results suggest that nursing assistance tools may prevent upper arm pain and improve the burden on the lower back among staff in schools for disabled children; however, these tools did not significantly prevent low back pain and depression.", "A single blind randomized controlled trial comparing two models of care for patients with acute simple low back pain.\n To compare two research-based models of care for acute low back pain and investigate the effect of the timing of physical intervention.\n National guidelines offer conflicting information on the delivery of physical treatment in the management of acute low back pain. The guidelines suggest two different models of care. Direct comparisons between these models are lacking in the literature. The present study aims to compare these approaches to the management of acute low back pain.\n Among 804 referred patients, 102 subjects met the specific admission criteria and were randomly assigned to an \"assess/advise/treat\" group or an \"assess/advise/wait\" group. The intervention consisted of biopsychosocial education, manual therapy, and exercise. Assessment of short-term outcome enables comparison to be made between intervention and advice to stay active. Assessment of long-term outcome enables comparison to be made between early and late intervention. Study outcomes of reported pain (Visual Analogue Scale), functional disability (the Roland and Morris Disability Questionnaire), mood (Modified Zung Self Rated Depression Score, Modified Somatic Perception Questionnaire, State-Trait Anxiety Inventory), general health (Euroqol), and quality of life (Short Form 36) were assessed at baseline, 6 weeks, 3 months, and 6 months.\n At 6 weeks, the assess/advise/treat group demonstrated greater improvements in disability, mood, general health, and quality of life than patients in the assess/advise/wait group (P < 0.05). Disability and pain were not significantly different between the groups at long-term follow up (P > 0.05). However, mood, general health, and quality of life remained significantly better in the assess/advise/treat group (P < 0.05).\n At short-term, intervention is more effective than advice on staying active, leading to more rapid improvement in function, mood, quality of life, and general health. The timing of intervention affects the development of psychosocial features. If treatment is provided later, the same psychosocial benefits are not achieved. Therefore, an assess/advise/treat model of care seems to offer better outcomes than an assess/advise/wait model of care.", "Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program.\n Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire.\n Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase.\n This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP.\n ClinicalTrials.gov: NCT00566930." ]

[ "9843104", "18164847", "17223873", "17635377", "7658819", "15057739", "12829675", "2196355", "20507841" ]

[ "Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis.", "A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118).", "Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy.", "A randomized, double-blind, placebo-controlled trial of lenalidomide in the treatment of moderately severe active Crohn's disease.", "Early antibiotic treatment in acute necrotising pancreatitis.", "Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo-controlled, double-blind trial.", "Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma.", "Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial.", "Results of a randomized, placebo-controlled safety and efficacy study of topical diclofenac 3% gel in organ transplant patients with multiple actinic keratoses." ]

[ "Toxic epidermal necrolysis (TEN) is associated with a 30% death rate. Tumour necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of TEN. Thalidomide is a potent inhibitor of TNF-alpha action. We did a double-blind, randomised, placebo-controlled study of thalidomide in TEN.\n The patients received a 5-day course of thalidomide 400 mg daily or placebo. The main endpoint was the progression of skin detachment after day 7. Secondary endpoints were the severity of the disease, evaluated with the simplified acute physiology score (SAPS), and the mortality. TNF-alpha and interleukin 6 were measured.\n The study was stopped because there was excess mortality in the thalidomide group--ten of 12 patients died compared with three of ten in the placebo group (Fisher's exact test with Katz's approximation, relative risk=2.78, p=0.03). After adjustment for SAPS, mortality remained significantly higher in the thalidomide group than in the placebo group (exact logistic regression mid-p=0.007; 95% CI for odds ratio 2.7 to infinity). Plasma TNF-alpha concentration was higher in the thalidomide group than the placebo group on day 2, though the difference was not significant (Wilcoxon rank-sum test p=0.07).\n Even though few patients were included, our data suggest that thalidomide is detrimental in TEN, possibly because of a paradoxical enhancement of TNF-alpha production.", "To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery.\n Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines.\n Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects.\n Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.", "Organ transplant recipients (OTR) are at high risk of developing nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/ Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments.\n To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia.\n Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference.\n At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group.\n Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population.", "Therapy targeted at tumour necrosis factor-alpha has an established role in Crohn's disease. Lenalidomide, an analogue of thalidomide, is an oral immunomodulatory agent with powerful antitumour necrosis factor-alpha properties. It is licensed for myeloma and myelodysplastic syndrome. Based upon reports of thalidomide efficacy, lenalidomide was evaluated in Crohn's disease.\n To evaluate the efficacy and safety of lenalidomide in subjects with moderately severe active Crohn's disease.\n In a multicentre, double-blind, placebo-controlled parallel group study 89 subjects were randomized to lenalidomide 25 mg daily, 5 mg daily or placebo. Subjects were treated for 12 weeks. The primary end point was a 70-point reduction in Crohn's Disease Activity Index.\n The overall clinical response rate was not significantly different between the three groups: lenalidomide 25 mg 26%, lenalidomide 5 mg 48% and placebo 39%. Lenalidomide was generally well tolerated with only one serious adverse event, a deep vein thrombosis, being attributed to treatment.\n Lenalidomide, an oral agent with antitumour necrosis factor-alpha properties, was not effective in active Crohn's disease in contrast to reports of benefit from thalidomide. The reasons for this lack of efficacy are speculative, other physiological activities may offset its action on inflammatory cytokines, or its antitumour necrosis factor-alpha action without apoptosis may be insufficient for activity in Crohn's disease.", "Despite improvements in surgical treatment and intensive care, mortality from severe acute pancreatitis remains high. We have carried out a randomised study of 60 consecutive patients with alcohol-induced necrotising pancreatitis to find out whether early antibiotic treatment can improve outcome. 30 patients were assigned cefuroxime (4.5 g/day intravenously) from admission. In the second group, no antibiotic treatment was given until clinical or microbiologically verified infection or after a secondary rise in C-reactive protein. The inclusion criteria were C-reactive protein concentration above 120 mg/L within 48 h of admission and low enhancement (< 30 Hounsfield units) on contrast-enhanced computed tomography. There were more infectious complications in the non-antibiotic than in the antibiotic group (mean per patient 1.8 vs 1.0, p = 0.01). The most common cause of sepsis was Staphylococcus epidermidis; positive cultures were obtained from pancreatic necrosis or the central venous line in 14 of 18 patients with suspected but blood-culture-negative sepsis. Mortality was higher in the non-antibiotic group (seven vs one in the antibiotic group; p = 0.03). Four of the eight patients who died had cultures from pancreatic necrosis positive for Staph epidermidis. We conclude that cefuroxime given early in necrotising pancreatitis is beneficial and may reduce mortality, probably by decreasing the frequency of sepsis.", "Antibiotic prophylaxis in necrotizing pancreatitis remains controversial. Until now, there have been no double-blind studies dealing with this topic.\n A total sample size of 200 patients was calculated to demonstrate with a power of 90% that antibiotic prophylaxis reduces the proportion of patients with infected pancreatic necrosis from 40% placebo (PLA) to 20% ciprofloxacin/metronidazole (CIP/MET). One hundred fourteen patients with acute pancreatitis in combination with a serum C-reactive protein exceeding 150 mg/L and/or necrosis on contrast-enhanced CT scan were enrolled and received either intravenous CIP (2 x 400 mg/day) + MET (2 x 500 mg/day) or PLA. Study medication was discontinued and switched to open antibiotic treatment when infectious complications, multiple organ failure sepsis, or systemic inflammatory response syndrome (SIRS) occurred. After half of the planned sample size was recruited, an adaptive interim analysis was performed, and recruitment was stopped.\n Fifty-eight patients received CIP/MET and 56 patients PLA. Twenty-eight percent in the CIP/MET group required open antibiotic treatment vs. 46% with PLA. Twelve percent of the CIP/MET group developed infected pancreatic necrosis compared with 9% of the PLA group (P = 0.585). Mortality was 5% in the CIP/MET and 7% in the PLA group. In 76 patients with pancreatic necrosis on contrast-enhanced CT scan, no differences in the rate of infected pancreatic necrosis, systemic complications, or mortality were observed.\n This study detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis.", "Temozolomide is an imidazotetrazine with a mechanism of action similar to dacarbazine and equivalent activity in melanoma. It is well tolerated and is a candidate for combination chemotherapy and schedule manipulation. In this study, we combined temozolomide with interferon alfa-2b and, separately, with thalidomide, and we administered temozolomide alone in a compressed schedule. The objectives of this randomized phase II, two-center study were to determine response rates, overall survival, and tolerability of the regimens in patients with advanced metastatic melanoma.\n One hundred eighty-one patients with metastatic melanoma were randomly assigned to receive up to six 4-weekly cycles consisting of temozolomide 200 mg/m2 every 8 hours for five doses, or temozolomide 200 mg/m2 daily for days 1 to 5 plus interferon alfa-2b 5 MU (million International Units) subcutaneously three times a week, or temozolomide 150 mg/m2 (increased after one cycle to 200 mg/m2) daily on days 1 to 5 plus thalidomide 100 mg daily days 1 to 28.\n The treatment arms were well balanced for known prognostic factors. Median survival was 5.3 months for 8-hourly temozolomide, 7.7 months for temozolomide/interferon, and 7.3 months for temozolomide/thalidomide; and 1-year survivals were 18%, 26%, and 24%, respectively. Response or disease stabilization occurred in 20% of patients (95% confidence interval [CI], 10% to 33%) given 8-hourly temozolomide, 21% (95% CI, 12% to 33%) given temozolomide/interferon, and 25% (95% CI, 15% to 38%) given temozolomide/thalidomide. Grade 3 or 4 nonhematologic toxicities were similar in each arm except for infection, which was more frequent with 8-hourly temozolomide. There were fewer instances of grade 3 or 4 myelotoxicity with temozolomide/thalidomide.\n Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.", "To determine whether prenatal corticosteroid therapy would reduce the incidence of neonatal necrotizing enterocolitis (NEC), we assigned a total of 466 women admitted in premature labor either to receive placebo (group A, n = 256), if delivery was expected to occur within 24 hours of admission, or to receive betamethasone (group B, n = 210) if delivery was expected to take place more than 24 hours after admission. All women were free of severe medical complications or drug therapy; cases of intrauterine growth retardation or premature rupture of the membranes were excluded. Their newborn infants, excluding malformed, congenitally infected, and growth-retarded infants, were enrolled in the study unless they had died before the age of 10 postnatal days. Babies born to group A mothers (n = 248) were further assigned to a treatment group (group A1, n = 130) receiving dexamethasone, 2 mg/kg/day by intravenous injection during the first 7 days of life, or to a control group (group A2, n = 118) receiving 10% dextrose solution placebo. Group B infants (prenatal betamethasone, n = 205) received neither treatment nor placebo. The incidence of NEC in group A1 was 6.9% (9/130), and in group A2 it was 14.4% (17/118) (p less than 0.05). In group B the incidence was 3.4% (7/205); this was much lower than in group A2 (p less than 0.01) and lower than in group A combined (10.4%) (p less than 0.01). There was no death from NEC and no surgical intervention among group B patients. The mortality rate for group A1 (11%) was lower than for group A2 (56%) (p less than 0.02). There were fewer indications for surgical intervention for NEC in group A1 than in group A2. Histologic studies confirmed bowel ischemia in all specimens analyzed. These data support the hypothesis that the incidence of NEC is significantly reduced after prenatal steroid treatment. Although postnatal therapy with steroids does not decrease the incidence as effectively as prenatal therapy, it improves clinical outcome of NEC.", "Increasing incidence rates of cutaneous malignancies, paralleling rising survival times of grafts and patients in organ transplant recipients, represents an escalating challenge for dermatologists worldwide. Especially, invasive squamous cell carcinomas (SCC) in immuno-compromised patients are characterized by significantly increased morbidity and mortality and characteristically outnumber basal cell carcinoma in this population. Effective management of actinic keratoses (AK) could help to prevent the further development of invasive SCC. Diclofenac in hyaluronic acid has previously shown to be an effective and well tolerated option for the treatment of AK in immuno-competent patients. However, its safety and efficacy in organ-transplant patients has not been evaluated in a controlled study so far. 32 organ transplant patients (kidney (+/- pancreas), liver, heart) screened at our specialized transplant dermatology outpatient clinic were found eligible and were randomized to either active treatment (24) or vehicle (8). Patients who had stable status of the transplanted graft in the 12 months prior to entering the study and >/= 3 AK lesions in a contiguous 50 cm2 area on the face, forehead, hands or balding scalp were eligible for inclusion in the study. Treatment of AK with 3% diclofenac in 2.5% hyaluronic acid or placebo twice daily was conducted over a total of 16 weeks, followed by a final evaluation 4 weeks after last application of the study drug. Biopsies were taken from the treated areas at the final visit to verify clinical clearance. Patients were assessed for safety variables that included adverse events, local skin reactions, laboratory results, dosage of immunosuppressive medication and indication of graft rejection. A 24 months follow up was conducted after the end of treatment. 87% (n = 28/32) of the patients completed the 16 week treatment phase and presented for final evaluation 4 weeks after end of treatment. In the diclofenac 3% gel treatment group, a complete clearance of AK lesions was achieved in 41% (9/22) compared to 0% (0/6) in the vehicle group. Side effects in most of the patients included a mild erythema and a mild to moderate swelling of the areas treated. No graft rejections or trends for a deterioration of graft function were detected. No meaningful trends were observed in laboratory results. In 55% of the previously cleared patients, new AK developed in the study area after an average of 9.3 months. None of these patients developed invasive SCC in the study area within 24 months of follow-up. This study demonstrated a greater lesion clearance rate of AKs in OTRs treated with diclofenac 3% gel than with vehicle. Despite recurrent AK in 55% of the previously cleared patients, the 24 month results showed no invasive SCC in this group. This study suggests that diclofenac 3% gel is not only an efficient and well tolerated treatment for multiple AKs in OTRs but also may prevent invasive SCC in these high-risk patients." ]

[ "12610718", "10870870", "20724402", "16585434", "16585435", "18794652", "17526456", "15933483", "15323587" ]

[ "Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study.", "A comparison of the effects of quetiapine ('seroquel') and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. PRIZE Study Group.", "Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.", "Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.", "Quetiapine addition to serotonin reuptake inhibitors in patients with severe obsessive-compulsive disorder: a double-blind, randomized, placebo-controlled study.", "Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study.", "Adding quetiapine to SRI in treatment-resistant obsessive-compulsive disorder: a randomized controlled treatment study.", "A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors." ]

[ "Switching patients from one antipsychotic to another can lead to tolerability problems or transient symptom exacerbations. It is important to compare switching strategies to determine which methods produce the best possible patient outcomes.\n To investigate the efficacy, safety and tolerability of three dosing strategies for switching chronic, stable patients with schizophrenia from current oral antipsychotic monotherapy to once-daily oral aripiprazole monotherapy.\n Patients in this 8-week, open-label, outpatient study were randomized to: 1). immediate initiation of 30 mg/day aripiprazole with simultaneous immediate discontinuation of current antipsychotic; 2). immediate initiation of 30 mg/day aripiprazole while tapering off current antipsychotic over 2 weeks; or 3). up-titrating aripiprazole to 30 mg/day over 2 weeks, while simultaneously tapering off current antipsychotic. Efficacy assessments included PANSS, CGI-S, and CGI-I scores. Safety assessments included: adverse events (AEs) recording, evaluation of extrapyramidal symptoms (EPS), vital signs, ECG, and clinical laboratory tests.\n Efficacy with aripiprazole was maintained during the study with numerical improvements compared with baseline in all three groups. The overall incidence of AEs was broadly comparable across all groups, and AEs were generally mild to moderate in severity and time-limited. Discontinuations due to AEs were comparable across the groups. No deterioration in EPS occurred in any group. The reduction in body weight and plasma prolactin levels following switch to aripiprazole were comparable across the three groups.\n Any of the three strategies evaluated can be used safely for switching patients to aripiprazole from antipsychotic monotherapy. Furthermore, patients' symptoms may continue to improve after switching to aripiprazole.", "Quetiapine ('Seroquel') is a well-tolerated, novel, atypical antipsychotic with consistent efficacy in the treatment of schizophrenia. To date, no clinical studies have evaluated the effect of quetiapine in patients who only partially respond to conventional antipsychotics, yet this type of patient is most frequently seen by psychiatrists. Therefore, this international, multicentre, double-blind study was conducted to compare the efficacy and tolerability of 8 weeks' treatment of quetiapine 600 mg/day with haloperidol 20 mg/day in 288 patients who had a history of partial response to conventional antipsychotics and displayed a partial or no response to 1 month of fluphenazine (20 mg/day) treatment. Patients on quetiapine tended to have greater improvement than those on haloperidol in the primary efficacy measure, mean Positive and Negative Symptom Scale (PANSS) score, after 4 weeks' treatment (-9.05, -5.82, respectively, P = 0.061) and at study end (-11.50, -8.87, respectively, P = 0.234). Similarly, there was a trend towards patients on quetiapine demonstrating greater improvements in the secondary efficacy measures (Clinical Global Impression, PANSS subscale and Brief Psychiatric Rating Scale scores) [week 4 (baseline) to week 12 (end)], but the difference between treatments did not reach significance. Significantly more patients on quetiapine than on haloperidol showed a clinical response-patient response rates, defined as > 20% reduction in PANSS total score between weeks 4 and 12, were 52.2% for quetiapine and 38.0% for haloperidol (P = 0.043). Patients receiving quetiapine required less anticholinergic medication (P < 0.011), had greater reduction in extrapyramidal symptoms (EPS) (P = 0.005) and fewer treatment-emergent EPS-related adverse events compared to those on haloperidol (P < 0.001). Serum prolactin concentrations were elevated at the end of fluphenazine treatment in 73% of patients. Between weeks 4 and 12, elevated serum prolactin concentrations significantly decreased in quetiapine-treated patients compared to those receiving haloperidol (P < 0.001). At the end of quetiapine treatment, 83% of patients had normal prolactin levels while only 21% of patients receiving haloperidol were within the normal range. These results suggest that quetiapine may make a valuable contribution to the management of patients with a history of partial response to conventional antipsychotics.", "To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment.\n 12 month randomised, double blind, placebo controlled trial.\n Early psychosis outpatient clinics in Hong Kong.\n 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis.\n Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred.\n Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds.\n 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; chi(2)=3.20, df=1; P=0.07).\n In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year. Trial registration Clinical trials NCT00334035.", "When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.\n Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).\n Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.\n For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.", "In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic.\n Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason.\n The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168).\n Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.", "Although many patients with obsessive-compulsive disorder (OCD) benefit from treatment with serotonin reuptake inhibitors (SRIs), it is estimated that 40% to 60% of them do not respond. The objective of the present study was to evaluate the efficacy of quetiapine added to baseline treatment with SRIs for the treatment of OCD in severely ill adult subjects.\n Forty patients (21 men, 19 women) with primary OCD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria participated in a 12-week, double-blind, placebo-controlled trial. They were randomly assigned to dosages of quetiapine titrated up to 400 mg/d (n = 20) or to placebo (n = 20) in addition to their SRI treatment. During the continuation phase (weeks 6-12), subjects received different dosages between 400 and 600 mg/d depending on clinical response. At entry, all patients were unresponsive to at least 1 course of at least 12 weeks of treatment with SRIs at defined doses. The total Yale-Brown Obsessive-Compulsive Scale score was the primary efficacy parameter.\n Intention-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Yale-Brown Obsessive-Compulsive Scale score of 5.2 +/- 5.4 in the quetiapine group and 3.9 +/- 4.9 in the placebo group. The analysis of treatment effects between the 2 groups showed no significant difference. There were no significant group differences in any of the other self-rating scales or clinician-administered rating scales.\n In this study, augmentation of SRI treatment with quetiapine in severe OCD had no additional effect.", "Schizophrenia is a devastating psychiatric disorder. Clozapine has long been the gold standard for treatment of patients with treatment-resistant schizophrenia; however, some patients are only partially responsive to clozapine treatment. Augmentation of clozapine treatment might enhance its effectiveness in partial responders, but only a few studies have investigated possible augmentation strategies. This study compared the effectiveness and tolerability of the combination of amisulpride and clozapine with the combination of quetiapine and clozapine in patients who were only partially responsive to clozapine monotherapy. Fifty-six treatment-resistant patients who were partially responsive to clozapine were randomly assigned to receive amisulpride or quetiapine along with an ongoing stable dose of clozapine. Fifty patients completed the study. Patients were evaluated at baseline and at the first, third, sixth, and eighth weeks. Efficacy measures consisted of the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Clinical Global Impression (CGI) scale. Tolerability and adverse effects were assessed with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and the Simpson Angus Scale (SAS). A substantial improvement occurred in both groups by the end of the eighth week; however, the improvement associated with amisulpride was significantly greater than that seen with quetiapine. This difference was noted as early as the third week of follow-up in terms of CGI scores, and by the sixth week with regard to BPRS, SANS, and SAPS scores. Both drugs were well tolerated, as measured by UKU and SAS. Improvement favoring clozapine+amisulpride could be attributed to the selective D2/D3 binding property of amisulpride, which had an additional effect in improving symptoms of schizophrenia. The authors concluded that amisulpride seems to be effective and well tolerated for augmentation purposes in clozapine-resistant patients.", "This study aimed to determine the efficacy and tolerability of adding quetiapine to a serotonin reuptake inhibitor in treatment-resistant obsessive-compulsive disorder (OCD). Twenty-one adult treatment-resistant OCD patients were randomized to 16 weeks of augmentation with either quetiapine (n = 11) or placebo (n = 10). Patients with significant comorbidities, including tic-spectrum disorders, were not included. The treatment was well tolerated, with only one premature dropout in each treatment-group. The primary analysis showed that individuals in the quetiapine-treated group showed a 14% mean improvement in baseline Yale-Brown Obsessive-Compulsive Scale scores at study endpoint compared with a 6% improvement in those treated with placebo, but this difference did not reach statistical significance (F<1). Three patients treated with quetiapine met criteria for clinical response, compared to one patient who was treated with placebo. Larger studies are needed to explore the efficacy of second generation antipsychotics, such as quetiapine, when used as adjunct treatment in resistant OCD.", "Although serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD), 40% to 60% of patients do not respond to this treatment. This study was conducted to evaluate the efficacy and tolerability of quetiapine in addition to an SRI for treatment-refractory patients with OCD.\n Forty patients (10 men/30 women, mean +/- SD age = 35.2 +/- 12.1 years; range, 18-60 years) with primary OCD according to DSM-IV criteria who were recruited between February 2001 and December 2002 were randomly assigned in an 8-week, double-blind, placebo-controlled trial to receive dosages titrated upward to 300 mg/day of quetiapine (N = 20) or placebo (N = 20) in addition to their SRI treatment. At entry, all patients were unresponsive to courses of treatment with at least 2 different SRIs at a maximum tolerated dose for 8 weeks. During the study, primary efficacy was assessed according to change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A responder was defined as having a final Clinical Global Impressions-Improvement scale rating of \"very much improved\" or \"much improved\" and a decrease of > or = 35% in Y-BOCS score.\n An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Y-BOCS score of 9.0 +/- 7.0 (31%) in the quetiapine group and 1.8 +/- 3.4 (7%) in the placebo group (F=16.99, df=1,38; p <.001). Eight (40%) of 20 patients in the quetiapine group and 2 (10%) of 20 patients in the placebo group were responders (chi2=4.8, df=1, p=.028). The most common side effects in the quetiapine group were somnolence, dry mouth, weight gain, and dizziness.\n The results of this study show that quetiapine in addition to an SRI is beneficial for patients with OCD who do not respond to SRI treatment alone." ]

[ "9596436", "671684", "8850394", "16772625", "10625156", "9025128", "8006266", "8350885", "9671087" ]

[ "Effectiveness of mechanical versus manual chest compressions in out-of-hospital cardiac arrest resuscitation: a pilot study.", "External cardiac compression. A randomized comparison of mechanical and manual techniques.", "Active compression-decompression cardiopulmonary resuscitation does not improve survival in patients with prehospital cardiac arrest in a physician-manned emergency medical system.", "Manual chest compression vs use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest: a randomized trial.", "Active compression-decompression cardiopulmonary resuscitation: a population-based, prospective randomised clinical trial in out-of-hospital cardiac arrest.", "Active compression-decompression resuscitation: a prospective, randomized study in a two-tiered EMS system with physicians in the field.", "Active compression-decompression resuscitation: effect on resuscitation success after in-hospital cardiac arrest.", "A preliminary study of cardiopulmonary resuscitation by circumferential compression of the chest with use of a pneumatic vest.", "The United Kingdom pre-hospital study of active compression-decompression resuscitation." ]

[ "A prospective, randomized effectiveness trial was undertaken to compare mechanical versus manual chest compressions as measured by end-tidal CO2 (ETCO2) in out-of-hospital cardiac arrest patients receiving advanced cardiac life support (ACLS) resuscitation from a municipal third-service, emergency medical services (EMS) agency. The EMS agency responds to approximately 6,700 emergencies annually, 79 of which were cardiac arrests in 1994, the study year. Following endotracheal intubation, all cardiac arrest patients were placed on 100% oxygen via the ventilator circuit of the mechanical cardiopulmonary resuscitation (CPR) device. Patients were randomized to receive mechanical CPR (TCPR) or human/manual CPR (HCPR) based on an odd/even day basis, with TCPR being performed on odd days. ETCO2 readings were obtained 5 minutes after the initiation of either TCPR or HCPR and again at the initiation of patient transport to the hospital. All patients received standard ACLS pharmacotherapy during the monitoring interval with the exception of sodium bicarbonate. CPR was continued until the patient was delivered to the hospital emergency department. Age, call response interval, initial electrocardiogram (ECG) rhythm, scene time, ETCO2 measurements, and arrest outcome were identified for all patients. Twenty patients were entered into the study, with 10 in each treatment group. Three patients in the TCPR group were excluded. Measurements in the HCPR group revealed a decreasing ETCO2 during the resuscitation in 8 of 10 patients (80%) and an increasing ETCO2 in the remaining 2 patients. No decrease in ETCO2 was noted in the TCPR group, with 4 of 7 patients (57%) actually showing an increased reading and 3 of 7 patients (43%) showing a constant ETCO2 reading. The differences in the ETCO2 measurements between TCPR and HCPR groups were statistically significant. Both groups were similar with regards to call response intervals, patient ages, scene times, and initial ECG rhythms. One patient in the TCPR group was admitted to the hospital but later died, leaving no survivors in the study. TCPR appears to be superior to standard HCPR as measured by ETCO2 in maintaining cardiac output during ACLS resuscitation of out-of-hospital cardiac arrest patients.", "To compare the effectiveness of manual and mechanical chest compression during cardiopulmonary resuscitation, 50 patients who suffered cardiac arrest were randomly allocated to receive manual or mechanical chest compression. Randomization was performed after failure of initial resuscitative measures but within ten minutes after the onset of cardiac arrest (mean, 6.4 +/- 1.2 min). Ten patients from each group survived longer than one hour following resuscitation. Three from the mechanical group and two from the manual group were eventually able to leave the hospital. Thus mechanical compression appears comparable with manual compression when manual compression is performed under ideal conditions. Mechanical chest compression may be employed when trained personnel are not readily available or where manual compression is technically difficult to perform.", "To examine the efficacy of a new method of cardiac resuscitation, active compression-decompression cardiopulmonary resuscitation (ACD CPR), in prehospital cardiac arrest.\n Prospective, randomized, controlled trial.\n Physician-manned Mobile Intensive Care Unit (MICU) of a university hospital, serving a population of 200,000.\n Adult patients with prehospital nontraumatic cardiac arrest treated by the MICU.\n Patients were randomized to standard chest compression according to American Heart Association (AHA) recommendations (group 1, 30 patients) or to the new technique (group 2, 26 patients). ACD was performed by use of a hand-held suction device. In both groups, advanced life support was performed as recommended by the AHA.\n Rate of patients regaining a spontaneous circulation (ROSC), hospital discharge rate, and mean carbon dioxide content during resuscitation were recorded. ROSC rates in groups 1 and 2 were 40% and 38.5%, respectively. Four patients (13.3%) in group 1 and three patients (11.5%) in group 2 were discharged (group 1 v group 2: n.s.). Anatomic conditions precluded the application of ACD CPR in 5 patients. The new technique was found to impose greater physical efforts than STD CPR. Capnography was performed in 23 patients (mean value: STD CPR: 11.9 +/- 4.7 mmHg, ACD CPR: 13.7 +/- 4.9 mmHg [n.s.]).\n ACD CPR did not improve, outcome and practical performance was complicated. Therefore, this technique should not be performed routinely, or without strict supervision in prehospital cardiac arrest.", "High-quality cardiopulmonary resuscitation (CPR) may improve both cardiac and brain resuscitation following cardiac arrest. Compared with manual chest compression, an automated load-distributing band (LDB) chest compression device produces greater blood flow to vital organs and may improve resuscitation outcomes.\n To compare resuscitation outcomes following out-of-hospital cardiac arrest when an automated LDB-CPR device was added to standard emergency medical services (EMS) care with manual CPR.\n Multicenter, randomized trial of patients experiencing out-of-hospital cardiac arrest in the United States and Canada. The a priori primary population was patients with cardiac arrest that was presumed to be of cardiac origin and that had occurred prior to the arrival of EMS personnel. Initial study enrollment varied by site, ranging from late July to mid November 2004; all sites halted study enrollment on March 31, 2005.\n Standard EMS care for cardiac arrest with an LDB-CPR device (n = 554) or manual CPR (n = 517).\n The primary end point was survival to 4 hours after the 911 call. Secondary end points were survival to hospital discharge and neurological status among survivors.\n Following the first planned interim monitoring conducted by an independent data and safety monitoring board, study enrollment was terminated. No difference existed in the primary end point of survival to 4 hours between the manual CPR group and the LDB-CPR group overall (N = 1071; 29.5% vs 28.5%; P = .74) or among the primary study population (n = 767; 24.7% vs 26.4%, respectively; P = .62). However, among the primary population, survival to hospital discharge was 9.9% in the manual CPR group and 5.8% in the LDB-CPR group (P = .06, adjusted for covariates and clustering). A cerebral performance category of 1 or 2 at hospital discharge was recorded in 7.5% of patients in the manual CPR group and in 3.1% of the LDB-CPR group (P = .006).\n Use of an automated LDB-CPR device as implemented in this study was associated with worse neurological outcomes and a trend toward worse survival than manual CPR. Device design or implementation strategies require further evaluation.\n clinicaltrials.gov Identifier: NCT00120965.", "Different mechanical devices have been developed to improve cardiopulmonary resuscitation (CPR). The aim of this study was to evaluate active compression-decompression (ACD) CPR applied by Emergency Medical Service (EMS) in a defined population. The Trondheim region EMS (population 154,000) employs simultaneous paramedic and physician response. Upon decision to treat, patients with cardiac arrest of presumed cardiac origin were allocated to ACD CPR (CardioPump) or standard CPR by drawing a random number tag. Outcome in each patient was determined on a 5 point ordinal scale (no clinical improvement = 1, survival to discharge = 5). In 4 years, CPR was attempted in a total of 431 cardiac arrests, 54 patients (13%) survived to discharge; 302 patients with similar baseline characteristics were randomised. The prevalence of bystander CPR was 57% and the median call-arrival interval 9 min. By intention to treat, the mean score in the standard CPR group was 2.51 and 17/145 patients (12%) survived. The mean score in the ACD CPR group was 2.53 (P = 0.9) and 20/157 patients (13%) survived. Cerebral outcome was similar in the two groups. Among the 145 ACD patients, the technique was successfully applied in 110, found inapplicable in 35 and in seven patients chest compressions were unnecessary. This is the largest, single-centre, randomised, population based study of ACD CPR in out-of-hospital cardiac arrest to date. Even when considering a wider outcome spectrum than crude survival, we found no evidence of clinical benefit. In a quarter of cases ACD CPR was inapplicable, further limiting its potential usefulness.", "Improved cardiopulmonary circulation with active compression-decompression cardiopulmonary resuscitation (ACD-CPR) has been demonstrated in studies using different animal models and a small number of humans in cardiac arrest (CA). However, prehospital studies have shown both positive and no extra benefit of ACD-CPR on return of spontaneous circulation (ROSC), hospital admission and discharge rates. The aim of our prospective study was to compare standard manual CPR (S-CPR) with ACD-CPR as the initial technique of resuscitating patients with out-of-hospital CA, with respect to survival rates and neurological outcome. Patients with out-of-hospital CA treated by emergency medical services (EMS) personnel were randomly assigned to one of two groups (ACD-CPR versus S-CPR). Time intervals to key measures were documented by means of on-line tape-recording. Neurological outcome was assessed using standard scoring systems (cerebral and overall performance categories (CPC and OPC)). A total of 220 patients (S-CPR, n = 114: ACD-CPR, n = 106) were included in the study in a random order. The treatment groups were similar with respect to age, sex, time interval from collapse to CPR, defibrillation and first adrenaline medication. There was no difference between the ACD group and the standard CPR group in terms of ROSC (50.9% vs. 59.6%), hospital admission (33% vs. 33.3%), hospital discharge (16% vs. 14%), or CPC and OPC (1.82 vs. 2.13 and 2.06 vs. 2.25, respectively). Concerning complications of CPR, there was no difference between the groups. In our two-tiered EMS system with physician-staffed ambulances, ACD-CPR neither improved nor impaired survival rates and neurological prognosis in patients with out-of-hospital cardiac arrest. The new CPR technique did not increase the complications associated with the resuscitation effort.", "The purpose of this study was to test the hypothesis that active compression-decompression would improve resuscitation success in human subjects after cardiac arrest.\n Active compression-decompression cardiopulmonary resuscitation is a new method that improves cardiopulmonary hemodynamic function in animal models and humans after cardiac arrest.\n We conducted a prospective randomized clinical trial in patients with in-hospital cardiac arrest. Patients were assigned to receive standard manual or active compression-decompression cardiopulmonary resuscitation. The primary study end points were spontaneous return of circulation, 24-h survival and survival to hospital discharge.\n Fifty-three consecutive patients after cardiac arrest undergoing 64 resuscitation attempts were studied (30 women, 23 men; mean [+/- SD] age 71 +/- 13 years, range 38 to 96). Spontaneous return of circulation was observed in 24 (47%) of 53 patients and was increased in patients receiving active compression-decompression compared with those receiving standard manual cardiopulmonary resuscitation (15 [60%] of 25 vs. 9 [32%] of 28, respectively, p = 0.042); 24-h survival was increased (12 [48%] of 25 vs. 6 [21%] of 28, respectively, p = 0.041); and there was a trend toward improved survival to hospital discharge (6 [24%] of 25 vs. 3 [11%] of 28, respectively, p = 0.198) when active compression-decompression was compared with standard manual cardiopulmonary resuscitation.\n Active compression-decompression cardiopulmonary resuscitation improves return of spontaneous circulation and 24-h survival after in-hospital cardiac arrest. Active compression-decompression cardiopulmonary resuscitation appears to be a beneficial adjunct to standard manual cardiopulmonary resuscitation.", "More than 300,000 people die each year of cardiac arrest. Studies have shown that raising vascular pressures during cardiopulmonary resuscitation (CPR) can improve survival and that vascular pressures can be raised by increasing intrathoracic pressure.\n To produce periodic increases in intrathoracic pressure, we developed a pneumatically cycled circumferential thoracic vest system and compared the results of the use of this system in CPR (vest CPR) with those of manual CPR. In phase 1 of the study, aortic and right-atrial pressures were measured during both vest CPR (60 inflations per minute) and manual CPR in 15 patients in whom a mean (+/- SD) of 42 +/- 16 minutes of initial manual CPR had been unsuccessful. Vest CPR was also carried out on 14 other patients in whom pressure measurements were not made. In phase 2 of the study, short-term survival was assessed in 34 additional patients randomly assigned to undergo vest CPR (17 patients) or continued manual CPR (17 patients) after initial manual CPR (duration, 11 +/- 4 minutes) had been unsuccessful.\n In phase 1 of the study, vest CPR increased the peak aortic pressure from 78 +/- 26 mm Hg to 138 +/- 28 mm Hg (P < 0.001) and the coronary perfusion pressure from 15 +/- 8 mm Hg to 23 +/- 11 mm Hg (P < 0.003). Despite prolonged unsuccessful manual CPR, spontaneous circulation returned with vest CPR in 4 of the 29 patients. In phase 2 of the study, spontaneous circulation returned in 8 of the 17 patients who underwent vest CPR as compared with only 3 of the 17 patients who received continued manual CPR (P = 0.14). More patients in the vest-CPR group than in the manual-CPR group were alive 6 hours after attempted resuscitation (6 of 17 vs. 1 of 17) and 24 hours after attempted resuscitation (3 of 17 vs. 1 of 17), but none survived to leave the hospital.\n In this preliminary study, vest CPR, despite its late application, successfully increased aortic pressure and coronary perfusion pressure, and there was an insignificant trend toward a greater likelihood of the return of spontaneous circulation with vest CPR than with continued manual CPR. The effect of vest CPR on survival, however, is currently unknown and will require further study.", "This prospective, controlled trial with crossover group design compares the effectiveness of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of victims of prehospital cardiac arrest. In three UK cities, victims of non-traumatic, out of hospital cardiac arrest, over the age of 8 years received either standard or ACD-CPR on arrival of ambulance personnel. Main outcome measures were return of spontaneous circulation, survival to be admitted to the intensive care unit, survival to hospital discharge, and neurological outcome. A total of 576 patients (STD-CPR, n=309; ACD-CPR, n=267) were analysed. The treatment groups were similar with respect to age, gender, proportion of witnessed arrests, initial cardiac rhythm, and call to advanced life support interval. The proportion of patients receiving bystander CPR was higher in the ACD group (37.1% vs. 28.5%; P=0.028). The interval between collapse and defibrillation was longer in the ACD group (12.3 min vs. 10.4 min; P=0.028). There was no difference between the STD-CPR and ACD-CPR groups in survival to admission to the intensive care unit (13.6% vs. 13.8%; P=0.93) or hospital discharge (4.8% vs. 6.0%; P=0.67). There was no difference between the groups with respect to the neurological outcome of those patients surviving to hospital discharge. Analysis of important subgroups also showed no benefit for ACD-CPR. We conclude that there was no improvement in outcome with ACD-CPR when used by ambulance personnel in Cardiff and Portsmouth." ]

[ "10535880", "12072596", "8391042", "15489585", "19052125", "7489345", "11580151", "12063985", "8621174" ]

[ "A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia.", "High sustained response rate in patients with histologically mild (low grade and stage) chronic hepatitis C infection. A randomized, double blind, placebo controlled trial of interferon alpha-2b with and without ribavirin.", "Randomised trial of lymphoblastoid alpha-interferon in chronic hepatitis C. Effects on inflammation, fibrogenesis and viremia.", "Histological response in patients treated by interferon plus ribavirin for hepatitis C virus-related severe fibrosis.", "Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon.", "Comparative study of two high doses of lymphoblastoid interferon in the treatment of chronic hepatitis C: influence on the levels of ALT, viraemia and histologic activity.", "Maintenance therapy with gradual reduction of the interferon dose over one year improves histological response in patients with chronic hepatitis C with biochemical response: results of a randomized trial.", "Interferon-alpha-2b and ribavirin for retreatment of chronic hepatitis C.", "A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C." ]

[ ": At least half of patients with chronic hepatitis C virus (HCV) fail to respond to interferon or interferon/ribavirin therapy. Histological improvement is observed in some nonresponders. We conducted a randomized, controlled trial to determine if maintenance interferon therapy could prevent histological progression in this subset of nonresponders.\n Fifty-three patients with chronic HCV were enrolled. All were HCV-RNA positive after 6 months of treatment with interferon alfa-2b but had a histological response. Twenty-seven of the patients were randomly assigned to continue interferon (3 MU 3 times weekly) for 24 months; 26 patients discontinued treatment and were observed prospectively. Alanine aminotransferase (ALT) level and HCV-RNA titer were monitored, and liver biopsy was repeated every 12 months.\n Before interferon therapy, the 2 groups were well matched for all demographic factors, serum ALT (94.0 +/- 15.6), log HCV-RNA titer (5. 85 +/- 0.15 copies/mL), histology score (9.5 +/- 0.2), and percentage with cirrhosis (25%). After 6 months of treatment, significant reductions (P < 0.05) in serum ALT level (62.6 +/- 9.6), log HCV-RNA titer (4.79 +/- 0.13 copies/mL), and hepatic inflammation (4.0 +/- 0.2) were observed. These improvements were maintained in the patients randomized to continue interferon. Stopping treatment was associated with an increase in serum ALT, log HCV-RNA, and hepatic inflammation back to baseline. After 30 months of treatment, mean fibrosis score declined from 2.5 to 1.7 and 80% of patients had histological improvement (P < 0.03). Discontinuation of interferon was associated with an increase in mean fibrosis score from 2.2 to 2.4 and worsening of hepatic histology in 30% of patients (P < 0.01).\n These data support the hypothesis that maintenance interferon may prevent histological progression of chronic HCV in patients who remain viremic.", "To evaluate the efficacy and safety of therapy for patients with histologically mild hepatitis C virus (HCV) liver disease.\n A randomized, double blind, placebo controlled trial of interferon alpha-2b with or without ribavirin.\n Regional and university hospitals.\n One hundred and sixteen treatment naive patients with mild chronic HCV infection. Mild HCV infection was defined according to Knodell as a grade score of > or = 1 and < or = 6 and a stage score of < or = 1.\n Interferon alpha-2b (3 MU three times weekly) for 52 weeks in combination with either ribavirin or a matched placebo.\n The study endpoint was the absence of HCV RNA in plasma and liver tissue 26 weeks post-treatment. In addition, liver histology was compared pre- and post-treatment.\n Combination therapy was superior to interferon monotherapy, with a virological sustained response rate of 54% (31/57) and 20% (12/59), respectively, in both serum and liver tissue (P = 0.001). The sustained response rate was higher with combination therapy than monotherapy both in genotype non-1 (81% vs 36%) and in genotype 1 (28% vs 4%). There was a significant improvement in mean grade score in all sustained responders, irrespective of treatment arm.\n Combination therapy with interferon and ribavirin was safe and as effective in patients with histologically mild HCV infection as previously reported for more advanced disease.", "Seventy-two patients with chronic hepatitis C were included in a randomised trial of lymphoblastoid interferon versus no treatment. Thirty-six patients entered each group. Interferon was given in a step-down schedule for 12 months. Aminotransferase activities became normal during treatment in 30 of 36 (83.3%) treated patients, but in only 1 out of 36 (2.7%) non-treated cases (p < 0.001). However, a reactivation of the disease during the interferon course was observed in 12 patients after a mean of 5.58 +/- 1.55 months of therapy, and a post-treatment relapse was observed in 5 additional cases. The remaining 13 patients (36%) had sustained normalization of the aminotransferase levels for 15.27 +/- 10.34 months (range 3-30) after discontinuation of interferon, thus representing a long-term sustained remission of the disease. Knodell's histological activity index decreased in all treatment patients, except for 3 non-responders (91.5%), but in only 9 of 36 non-treated cases (25%) (p < 0.001). Procollagen type III peptide levels normalized in most cases (83%) with a sustained response. A significant decrease in the detection of hepatitis C virus RNA was observed in patients with a sustained response (p < 0.05). Anti-interferon antibodies were only detected in one non-responder. Thus, interferon diminishes inflammatory and fibrogenic activity in the majority of patients with chronic hepatitis C and abolishes viremia in most of the patients with a sustained response.", "Studies of viral hepatitis C have suggested that fibrosis can regress, at least in patients with sustained virological response. A recent study suggested that cirrhosis was reversible in sustained and non-virological responders.\n To study fibrosis progression rate and cirrhosis reversion in patients treated for severe fibrosis with interferon or interferon + ribavirin.\n Ninety-nine patients were treated with interferon + ribavirin and 64 with interferon. The Metavir fibrosis score and the semiquantitative fibrosis score (SFS) were used to assess fibrosis.\n In sustained responders, fibrosis progression rate decreased from 0.26 Metavir unit (interquartile range: 0.19-0.34) to -0.67 (-0.67 to 0) (P < 0.0001) and from 0.81 SFS unit (0.48-1.13) to -1.33 (-3.67 to 0) (P < 0.0001). In non-responders, fibrosis progression rate decreased from 0.25 Metavir unit (0.17-0.33) before treatment to 0 (0-0) during treatment (P = 0.002) and from 0.63 SFS unit (0.49-1.12) to 0 (-2.67-1.33) (P = 0.18). Six out of 18 (33%) sustained virological responders and four of 43 (9%) non-responders regressed from cirrhosis (F4) to severe fibrosis (F3) (P = 0.058). No patient with cirrhosis had a decrease of Metavir fibrosis score of 2 points.\n Interferon can slow fibrosis progression in sustained virological responders with severe fibrosis. In patients with a non-virological response and treated for 12 months the fibrosis progression rate was nil, meaning that only fibrosis stabilization could be obtained in these patients. Then, longer treatment duration (3-4 years) could be evaluated in non-virological responders.", "In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain.\n We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 microg per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of fibrosis (622 with noncirrhotic fibrosis and 428 with cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points.\n We randomly assigned the patients to receive peginterferon (517 patients) or no therapy (533 patients) for 3.5 years. The level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly (P<0.001) with treatment, but there was no significant difference between the groups in the rate of any primary outcome (34.1% in the treatment group and 33.8% in the control group; hazard ratio, 1.01; 95% confidence interval, 0.81 to 1.27; P=0.90). The percentage of patients with at least one serious adverse event was 38.6% in the treatment group and 31.8% in the control group (P=0.07).\n Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who had not had a response to initial treatment with peginterferon and ribavirin. (ClinicalTrials.gov number, NCT00006164.)\n 2008 Massachusetts Medical Society", "Ninety consecutive patients with chronic hepatitis C were included in a randomized, uncontrolled trial to compare the efficacy of two treatment regimens, 10 MU (group A) vs 5 MU (group B), of lymphoblastoid interferon, in a step-down schedule for 24 weeks. All of the patients had antibodies against the hepatitis C virus, and all but one were HCV RNA positive in serum. The origin of the infection was attributed to blood transfusion in 30 patients and classified as sporadic in 60 patients. During treatment reduction in the ALT levels as well as the elimination of viraemia was observed in both treated groups, although these changes did not correlate significantly with the interferon dose. Nine months after the end of therapy, a sustained response was achieved in 13.6% (12/88) of the patients. Relapse in group B (87.5%) was significantly higher than in group A (59.1%). The percentage of cases which remained with undetectable HCV RNA was significantly higher for the sustained responders (66.7%) than for the non-responders (11.8%) and relapser patients (2.4%). Repeated liver biopsies showed an overall significant reduction of all the subindices of histological activity from patients with sustained response, except for fibrosis. In short: the 10 MU dosing regimen of lymphoblastoid interferon was as efficient as the 5 MU dose as it brought about a similar improvement in ALT levels, histological activity and elimination of viraemia, albeit 10 MU proved significantly more effective in the prevention of a relapse among the responders after 24 weeks therapy.", "Our aim was to assess whether histological response was improved by continuing interferon-alpha (IFN) treatment in patients with chronic hepatitis C (HCV) with a biochemical response and no viral clearance after a usual IFN treatment.\n Fifty-seven patients with normal alanine aminotransferase (ALAT) levels and positive HCV RNA at the end of a 1 year IFN treatment were randomly assigned to either group 1 (n = 28) where IFN was stopped, or group 2 (n = 29) where IFN was continued for 1 more year with gradual reduction of the dose to keep serum ALAT activity below the upper limit of normal. Liver biopsies were obtained before, and then 6 months after the end of treatment.\n Knodell's index improved between paired biopsies in group 2 (8.2+/-2.4 vs. 5.5+/-2.1), but not in group 1 (8+/-2.3 vs. 6.5+/-2). In post-treatment biopsies, the METAVIR activity score was significantly lower in group 2 than in group 1 (0.7+/-0.2 vs. 1.1+/-0.3, P < 0.05). In group 2, an improvement of the METAVIR fibrosis score was observed (1.3+/-0.4 vs. 1.1+/-0.2), whereas fibrosis progressed in group 1 (1.3+/-0.4 vs. 1.6+/-0.4).\n Maintenance therapy by the minimal dose of IFN able to maintain biochemical response prevents histological progression in the sub-group of patients without virological response.", "Subjects with chronic hepatitis C who fail treatment with interferon-alpha are generally divided into two groups: \"relapsers\" who normalized serum aminotransferase activity and have undetectable viral RNA during treatment and \"non-responders\" who do not achieve these results. The aim of this study was to examine retreatment of such subjects.\n We studied 117 subjects with chronic hepatitis C who failed treatment with interferon-alpha, 87 of whom were \"non-responders\" and 30 \"relapsers.\" Retreatment was with either interferon-alpha-2b plus ribavirin for 48 weeks or with interferon-alpha-2b plus placebo for 24 weeks followed by 24 weeks of combined therapy.\n Sustained response rates, defined as undetectable viral RNA in serum 6 months after retreatment, were 53% in \"relapsers\" and 10% in \"non-responders\" (P < 0.005). There was no significant difference if ribavirin was given for 24 or 48 weeks. In \"non-responders\" infected with genotypes other than type 1, 42% achieved a sustained response compared to 5% infected with genotype 1 (P = 0.027; odds ratio 7.09).\n Treatment with interferon-alpha-2b plus ribavirin is effective in approximately 50% of \"relapsers\" and \"non-responders\" infected with non-type 1 genotypes of hepatitis C virus. This therapy is only marginally effective in \"non-responders\" infected with genotype 1a or 1b.", "Interferon treatment reduces the serum level of hepatitis C virus (HCV) and improves inflammatory activity, but relapse is frequently observed. In an attempt to develop a new therapeutic strategy that may reduce relapse and cure the disease, we evaluated the effect of corticosteroid priming on lymphoblastoid interferon alfa in an open randomized clinical trial. The level of HCV RNA increased significantly during corticosteroid priming (from 5.60 [median] to 21.0 x 10(5) Eq/mL; P = .0004) but decreased to the pretreatment level 4 weeks after cessation of corticosteroid (7.0 x 10(5) Eq/mL; P = .07). Sustained normalization of alanine transaminase (ALT) level and virus clearance, confirmed by negative results for HCV RNA using reverse-transcription nested polymerase chain reaction (PCR), were observed over a period of 6 months in 8 of 19 (42.1%) corticosteroid-primed patients, compared with 6 of 19 patients (31.6%) treated with interferon only. A \"rebound\" of ALT after the withdrawal of corticosteroid was observed in only 2 of 19 patients primed with corticosteroid, but both showed sustained responses. Multivariate analysis for factors predictive of the sustained response indicated that HCV titers measured immediately before interferon therapy and HCV genotype were statistically significant (P = .006 and P = .025, respectively). Our results indicated that corticosteroid priming has a marginal benefit over treatment with interferon alone and that large-scale clinical trials are necessary to determine whether interferon with corticosteroid priming is more effective than interferon alone." ]

[ "6996483", "10561618", "17028904", "9396885", "15694088", "12962946", "8960988", "16458640", "15288222" ]

[ "Midtrimester abortion by dilatation and evacuation versus intra-amniotic instillation of prostaglandin F2 alpha: a randomized clinical trial.", "Second-trimester uterine evacuation: A comparison of intra-amniotic (15S)-15-methyl-prostaglandin F2alpha and intravaginal misoprostol.", "A randomized comparison between intravaginal misoprostol and prostaglandin E2 for labor induction.", "A double-blind comparison of the safety and efficacy of intravaginal misoprostol and prostaglandin E2 to induce labor.", "Cervical priming with sublingual misoprostol vs. 15-methyl-prostaglandin F2alpha prior to surgical abortion.", "A comparison of isosorbide mononitrate and misoprostol cervical ripening before suction evacuation.", "Comparison of labor induction with misoprostol vs. oxytocin/prostaglandin E2 in term pregnancy.", "Cervical preparation using laminaria with adjunctive buccal misoprostol before second-trimester dilation and evacuation procedures: a randomized clinical trial.", "The role and comparison of two techniques of paracervical block for pain relief during suction evacuation for first-trimester pregnancy termination." ]

[ "To compare the safety and feasibility of midtrimester abortion by outpatient dilatation and evacuation (D-E) versus inpatient intra-amniotic instillation of prostaglandin F2 alpha (PGF2 alpha), we performed a randomized clinical trial with 100 subjects estimated to be 13 to 18 menstrual weeks pregnant. Subjects undergoing D-E abortion had significantly better compliance with the assigned treatment (100% vs. 88%, < 0.05) and less delay prior to abortion (mean 3.7 vs. 10.1 days, p < 0.001). Subjects receiving PGF2 alpha had a relative risk of sustaining a complication 5.7 times that of subjects undergoing D-E (95% confidence interval 2.1-15.3, p < 0.001). Subjects receiving PGF 2 alpha also had significantly higher rates of vomiting and diarrhea (p < 0.01). Midtrimester abortion by outpatient D-E appears to be more acceptable to women, faster, and safer than by instillation of PGF2 alpha.", "Our purpose was to compare the efficacy, safety, and adverse effects of intra-amniotically administered (15S)-15-methyl-prostaglandin F(2alpha) and intravaginally administered misoprostol for second-trimester uterine evacuation.\n Fifty-one patients were randomly assigned to receive either a single 2.5-mg intra-amniotic injection of (15S)-15-methyl-prostaglandin F(2)(alpha) (n = 26) or two 200-microg intravaginal doses of misoprostol (n = 25) at 12-hour intervals. The primary outcome measured was evacuation of the uterus within 24 hours.\n The mean time from initiation of termination to uterine evacuation was less in the prostaglandin group than in the misoprostol group (17.5 +/- 8.6 hours vs 22.3 +/- 12.5 hours), but this was not statistically significant (P >.05). The rate of successful fetal evacuation at 24 hours was significantly higher in the prostaglandin group than in the misoprostol group (88% vs 60%, P =.02). The complete-abortion rate and the incidence of adverse effects were similar in both groups.\n The use of an intra-amniotic injection of (15S)-15-methyl-prostaglandin F(2alpha) for midtrimester pregnancy termination is safe and is associated with a greater number of successful uterine evacuations within 24 hours, without an increase in adverse effects, than intravaginal administration of misoprostol.", "The aim of this randomized study was to compare the effectiveness, safety, and side effects of 6 h vaginal misoprostol versus vaginal prostaglandin E(2) (PGE(2)) for labor induction.\n Fifty microgram of misoprostol was given intravaginally in the misoprostol group (204 women), and 3 mg PGE(2) was given intravaginally in the PGE(2) group (211 women). In both groups, the dose was repeated every 6 h for a maximum of three doses, until active labor was achieved. Artificial rupture of membranes and oxytocin infusion was used during labor in both groups where it was indicated.\n The mean interval from the institution of labor induction to delivery was 11.3 +/- 8.6 h for the misoprostol group, and 15.7 +/- 9.3 h for PGE(2 )group (P < 0.05). In the misoprostol group, oxytocin was used less frequently, but there was a higher prevalence of tachysystole. No statistically significant differences were observed between the two groups as regard abnormal patterns of fetal heart rate, the mode of delivery, and the need for neonatal intervention.\n In conclusion, the intravaginal administration of 50 mug misoprostol at 6 h interval (maximum three doses) is comparable in safety, but more effective for induction of labor than 3 mg intravaginal PGE(2).", "Our purpose was to compare the safety and efficacy of intravaginally administered misoprostol versus prostaglandin E2 for labor induction in a double-blind, randomized trial.\n One hundred three patients with indications for labor induction (including prelabor rupture of membranes) were randomized and received either misoprostol 50 micrograms or prostaglandin E2 (dinoprostone) 3 mg intravaginally. The dose was repeated 6, 24, and 30 hours after the first dose until active labor was achieved. For proper blinding, the drugs were prepared as identical-looking vaginal tablets.\n With use of a random number-generated table 52 patients were allocated to the misoprostol group and 51 to the prostaglandin E2 group. After exclusion of 3 patients, 50 in each group were evaluated. Delivery within 24 hours after administration occurred more often in the misoprostol group (70% vs 46% in the prostaglandin E2 group, p = 0.009), and fewer patients in this group needed more than two doses (12% vs 30%, p = 0.027). No difference in cesarean section rate (12% vs 14%, p = 0.67), fetal heart rate anomalies (33% vs 34%, p = 0.89), tachysystole (8% vs 14%, p = 0.37), hyperstimulation syndrome (0% vs 2%, not significant), meconium passage (28% vs 18%, p = 0.22), and fetal outcome (Apgar score at 1 and 5 minutes, arterial and venous umbilical cord blood pH, transfer to neonatal intensive care unit) was noted between the two groups.\n Intravaginal misoprostol is a safe drug for labor induction with superior effectiveness compared with intravaginal prostaglandin E2.", "To compare the efficacy and tolerability of sublingual misoprostol with those of intramuscular 15-methyl-prostaglandin F2alpha (15-M-PG F2alpha) for cervical dilation prior to vacuum aspiration (VA) in first-trimester pregnancy termination.\n Sixty pregnant women requesting pregnancy termination between the 9th and 12th week were randomized to receive 400 microg of sublingual misoprostol or an intramuscular injection of 125 microg of 15-M-PG F2alpha 2 h prior to vacuum aspiration. Baseline cervical dilation prior to vacuum aspiration was measured using Hegar's dilators. Other variables assessed included procedure duration, intraoperative blood loss, and associated adverse effects. Patient acceptability was assessed by questionnaires completed at the time of discharge from the hospital.\n Mean cervical dilation at vacuum aspiration was significantly greater in the misoprostol group than in the 15-M-PG F2alpha group (8.8 vs. 7.6 mm; P<0.01), and preoperative adverse effects were significantly less frequent in the sublingual misoprostol group (P<0.05). However, procedure duration and intraoperative blood loss were similar in both groups. The acceptability rates were 93.3% in the sublingual misoprostol group and 76.6% in the 15-M-PG F2alpha group, respectively; however, 6.6% patients in the sublingual misoprostol group thought that the tablets had an unpleasant taste.\n Sublingual misoprostol appears to be an effective alternative to intramuscular 15-M-PG F2alpha for cervical dilation prior to vacuum aspiration in first trimester pregnancy. In addition, misoprostol is inexpensive and convenient to use and has higher patient acceptability rates.", "To compare the efficacy of a nitric oxide donor (isosorbide mononitrate) and a prostaglandin E1 analogue (misoprostol) for cervical priming before suction termination of pregnancy.\n This was a randomized, double blind, placebo-controlled trial. One hundred twenty-six healthy women requesting termination of pregnancy between 9 and 12 weeks' gestation were recruited. Women were randomized into three groups: control, isosorbide mononitrate, and misoprostol. All women were given moistened intravaginal study drugs (placebo, 40 mg of isosorbide mononitrate, or 400 microg of misoprostol) 4-6 hours before suction evacuation. Side effects were assessed 3 hours after drug administration. The cervical dilatation and the cumulative force required to dilate the cervix to 8 mm were measured by a cervical tonometer before suction evacuation. Operative blood loss was measured after sieving off the products of gestation.\n There were no differences in the baseline cervical dilatation, cumulative force, and operative blood loss between the isosorbide mononitrate and placebo groups. However, women in the misoprostol group had a significantly greater cervical dilatation, required less cumulative force, and had less blood loss than women in the isosorbide mononitrate or control group. The majority (more than 80%) of women in all three groups found their cervical priming agents acceptable.\n Intravaginal isosorbide mononitrate was less effective than misoprostol in cervical ripening before suction termination of pregnancy.", "To compare the efficacy and safety of intravaginal and oral misoprostol vs. oxytocin/prostaglandin E2 (PGE2) gel for third trimester labor induction.\n Two hundred twenty-four pregnant women were randomized to induction of labor either with misoprostol or oxytocin and PGE2 gel. Patients in the misoprostol group (n = 112) received 100 micrograms intravaginal misoprostol followed by 100 micrograms p.o. every 2 h. The oxytocin/PGE2 group consisted of 112 patients who underwent PGE2 cervical instillation 6 h before continuous oxytocin infusion. The perinatal, intrapartum and neonatal characteristics of both groups were determined.\n Induction to active phase of labor was successfully achieved in 96 women (85.7%) in the misoprostol group vs. 86 women (76.8%) in the oxytocin/PGE2 group, but the drug initiation-delivery interval was significantly shorter in the misoprostol group (9.2 +/- 2.4 h) than in the oxytocin/PGE2 group (15.2 +/- 3.2 h, P < 0.001). The incidence of adverse intrapartum outcomes was similar for both methods. Intravaginal misoprostol 100 micrograms followed by a single oral dose of 100 micrograms misoprostol safely produced labor and a vaginal delivery in 70% of patients. More than three tablets were required in only 10% of patients. There was a higher prevalence of cesarean section for failed induction in the oxytocin/PGE2 group than in the misoprostol group (13.4 vs. 6.3%, P < 0.001). The neonatal outcomes of both groups were also similar.\n Misoprostol is significantly more effective for labor induction than oxytocin/PGE2 gel. The maternal intrapartum and neonatal outcomes were the same for both induction regimens. From a clinical and perinatal perspective, misoprostol is an acceptable choice for labor induction.", "This study was undertaken to determine whether buccal misoprostol improves cervical preparation achieved with laminaria before second-trimester dilation and evacuation procedures.\n A randomized, double blind, placebo-controlled trial of preoperative cervical preparation with overnight laminaria and either buccal placebo or 400 microg buccal misoprostol approximately 90 minutes before second-trimester surgical abortion. Block randomization was used to provide balanced enrollment into 2 separate gestational age study groups: early (13-15(6/7)) and mid (16-20(6/7)) second trimester. Surgeons tested maximal cervical dilation by inserting the largest dilator that could be passed through the cervical os without force. Subject demographics and preprocedure symptoms were tracked.\n Groups were similar in regard to age, gravity, parity, delivery type, and gestational age. Data were analyzed from 125 women in the 13 to 15(6/7) (30 misoprostol, 32 placebo) and 16 to 20(6/7) (31 misoprostol, 32 placebo) gestational age groups. Overall, misoprostol treatment did not improve the initial mean dilation achieved with laminaria alone in either the 13 to 15(6/7) (46.0 fr +/- 5.0; placebo 45.0 fr +/- 6.2, P = .68) or 16 to 20(6/7) (50.9 fr +/- 5.6, placebo 48.9 fr +/- 5.2, P = .16) groups. However, a subanalysis of gestations 19 weeks or more demonstrated significantly greater dilation in the misoprostol group (53.6 fr fr +/- 5.3, placebo 48.5 fr +/- 5.0, P = .01). Subjects receiving misoprostol reported significantly more cramping than those receiving placebo (13-15(6/7) weeks misoprostol 25/30, 83%; placebo 17/32, 53%, P = .02; 16-20(6/7) week misoprostol 25/31, 81%, placebo 16/32, 50%, P = .02).\n Cervical dilation with laminaria is augmented by 400 microg buccal misoprostol in gestations 19 weeks or more, but not in earlier gestations. Misoprostol causes more abdominal cramping.", "This prospective study assessed the role and compared two techniques of paracervical block (PCB) for pain relief during suction evacuation for first-trimester termination of pregnancy following cervical priming with misoprostol. One-hundred and thirty-five women undergoing suction evacuation up to 12 weeks of gestation were randomized into three groups: (a) 5 mL of 1% lignocaine injected at the 4 and 8 o'clock positions of the vaginal vault; (b) 5 mL of 1% lignocaine injected at the 4 and 8 o'clock positions of the cervix and (c) no PCB. Pain scores during PCB, cervical dilatation and during and after suction evacuation were compared among the three groups. The sedation and satisfaction levels were also compared. There were no statistically significant differences in the pain levels during PCB, cervical dilatation and suction evacuation and in the satisfaction levels among the three groups. Patients with a lighter sedation level experienced more pain. In conclusion, PCB did not improve the pain levels during first-trimester suction termination of pregnancy after cervical priming with misoprostol and use of intravenous sedation, regardless of whether the local anaesthetic was injected into the cervix or the vaginal vault." ]

[ "19401897", "18547863", "17261562", "17654228", "17978833", "10362390", "19308790", "12627305", "16558514" ]

[ "A single 10-min bout of cold-water immersion therapy after strenuous plyometric exercise has no beneficial effect on recovery from the symptoms of exercise-induced muscle damage.", "Effect of water immersion methods on post-exercise recovery from simulated team sport exercise.", "Ice-water immersion and delayed-onset muscle soreness: a randomised controlled trial.", "Influence of cold-water immersion on indices of muscle damage following prolonged intermittent shuttle running.", "Effect of hydrotherapy on the signs and symptoms of delayed onset muscle soreness.", "Effects of cold water immersion on the symptoms of exercise-induced muscle damage.", "Effects of cold-water immersion on physical performance between successive matches in high-performance junior male soccer players.", "The use of magnetic resonance imaging to evaluate the effects of cooling on skeletal muscle after strenuous exercise.", "Effect of whirlpool therapy on the signs and symptoms of delayed-onset muscle soreness." ]

[ "The purpose of this study was to examine the effectiveness of a single bout of cold-water immersion on recovery from exercise-induced muscle damage. Eighteen physically active female volunteers (age 19.9 (+/-0.97 years), height 1.66 (+/-0.05 m), mass 63.7 (+/-10 kg), completed 10 sets of 10 counter-movement jumps to induce muscle damage and were randomly allocated to a control or treatment group. The treatment group was given a single 10-min bout of lower limb cold-water immersion therapy at 10 degrees C immediately following damage-inducing exercise. Indicators of muscle damage (plasma creatine kinase activity, perceived soreness and maximal voluntary contraction of the quadriceps) were assessed immediately prior to counter-movement jumps, and at 1, 24, 48, 72 and 96 h, following the damaging exercise. Significant (p = 0.05) time effects were recorded on all indicators of muscle damage, but there were no significant group or group x time interaction effects found on any of the measured variables. The results indicate that a single bout of cold-water immersion after a damaging bout of exercise has no beneficial effects on the recovery from exercise-induced muscle damage.", "This study aimed to compare the efficacy of hot/cold contrast water immersion (CWI), cold-water immersion (COLD) and no recovery treatment (control) as post-exercise recovery methods following exhaustive simulated team sports exercise. Repeated sprint ability, strength, muscle soreness and inflammatory markers were measured across the 48-h post-exercise period. Eleven male team-sport athletes completed three 3-day testing trials, each separated by 2 weeks. On day 1, baseline measures of performance (10 m x 20 m sprints and isometric strength of quadriceps, hamstrings and hip flexors) were recorded. Participants then performed 80 min of simulated team sports exercise followed by a 20-m shuttle run test to exhaustion. Upon completion of the exercise, and 24h later, participants performed one of the post-exercise recovery procedures for 15 min. At 48 h post-exercise, the performance tests were repeated. Blood samples and muscle soreness ratings were taken before and immediately after post-exercise, and at 24h and 48 h post-exercise. In comparison to the control and CWI treatments, COLD resulted in significantly lower (p<0.05) muscle soreness ratings, as well as in reduced decrements to isometric leg extension and flexion strength in the 48-h post-exercise period. COLD also facilitated a more rapid return to baseline repeated sprint performances. The only benefit of CWI over control was a significant reduction in muscle soreness 24h post-exercise. This study demonstrated that COLD following exhaustive simulated team sports exercise offers greater recovery benefits than CWI or control treatments.", "To determine if ice-water immersion after eccentric quadriceps exercise minimises the symptoms of delayed-onset muscle soreness (DOMS).\n A prospective randomised double-blind controlled trial was undertaken. 40 untrained volunteers performed an eccentric loading protocol with their non-dominant leg.\n Participants were randomised to three 1-min immersions in either ice water (5+/-1 degrees C) or tepid water (24 degrees C).\n Pain and tenderness (visual analogue scale), swelling (thigh circumference), function (one-legged hop for distance), maximal isometric strength and serum creatine kinase (CK) recorded at baseline, 24, 48 and 72 h after exercise. Changes in outcome measures over time were compared to determine the effect of group allocation using independent t tests or Mann-Whitney U tests.\n No significant differences were observed between groups with regard to changes in most pain parameters, tenderness, isometric strength, swelling, hop-for-distance or serum CK over time. There was a significant difference in pain on sit-to-stand at 24 h, with the intervention group demonstrating a greater increase in pain than the control group (median change 8.0 vs 2.0 mm, respectively, p = 0.009).\n The protocol of ice-water immersion used in this study was ineffectual in minimising markers of DOMS in untrained individuals. This study challenges the wide use of this intervention as a recovery strategy by athletes.", "The aim of this study was to assess the effects of cold-water immersion (cryotherapy) on indices of muscle damage following a bout of prolonged intermittent exercise. Twenty males (mean age 22.3 years, s = 3.3; height 1.80 m, s = 0.05; body mass 83.7 kg, s = 11.9) completed a 90-min intermittent shuttle run previously shown to result in marked muscle damage and soreness. After exercise, participants were randomly assigned to either 10 min cold-water immersion (mean 10 degrees C, s = 0.5) or a non-immersion control group. Ratings of perceived soreness, changes in muscular function and efflux of intracellular proteins were monitored before exercise, during treatment, and at regular intervals up to 7 days post-exercise. Exercise resulted in severe muscle soreness, temporary muscular dysfunction, and elevated serum markers of muscle damage, all peaking within 48 h after exercise. Cryotherapy administered immediately after exercise reduced muscle soreness at 1, 24, and 48 h (P < 0.05). Decrements in isometric maximal voluntary contraction of the knee flexors were reduced after cryotherapy treatment at 24 (mean 12%, s(x) = 4) and 48 h (mean 3%, s(x) = 3) compared with the control group (mean 21%, s(x) = 5 and mean 14%, s(x) = 5 respectively; P < 0.05). Exercise-induced increases in serum myoglobin concentration and creatine kinase activity peaked at 1 and 24 h, respectively (P < 0.05). Cryotherapy had no effect on the creatine kinase response, but reduced myoglobin 1 h after exercise (P < 0.05). The results suggest that cold-water immersion immediately after prolonged intermittent shuttle running reduces some indices of exercise-induced muscle damage.", "This study independently examined the effects of three hydrotherapy interventions on the physiological and functional symptoms of delayed onset muscle soreness (DOMS). Strength trained males (n = 38) completed two experimental trials separated by 8 months in a randomised crossover design; one trial involved passive recovery (PAS, control), the other a specific hydrotherapy protocol for 72 h post-exercise; either: (1) cold water immersion (CWI: n = 12), (2) hot water immersion (HWI: n = 11) or (3) contrast water therapy (CWT: n = 15). For each trial, subjects performed a DOMS-inducing leg press protocol followed by PAS or one of the hydrotherapy interventions for 14 min. Weighted squat jump, isometric squat, perceived pain, thigh girths and blood variables were measured prior to, immediately after, and at 24, 48 and 72 h post-exercise. Squat jump performance and isometric force recovery were significantly enhanced (P < 0.05) at 24, 48 and 72 h post-exercise following CWT and at 48 and 72 h post-exercise following CWI when compared to PAS. Isometric force recovery was also greater (P < 0.05) at 24, 48, and 72 h post-exercise following HWI when compared to PAS. Perceived pain improved (P < 0.01) following CWT at 24, 48 and 72 h post-exercise. Overall, CWI and CWT were found to be effective in reducing the physiological and functional deficits associated with DOMS, including improved recovery of isometric force and dynamic power and a reduction in localised oedema. While HWI was effective in the recovery of isometric force, it was ineffective for recovery of all other markers compared to PAS.", "Cryotherapy is an effective treatment for acute sports injury to soft tissue, although the effect of cryotherapy on exercise-induced muscle damage is unclear. The aim of this study was to assess the effects of cold water immersion on the symptoms of exercise-induced muscle damage following strenuous eccentric exercise. After performing a bout of damage-inducing eccentric exercise (eight sets of five maximal reciprocal contractions at 0.58 rad x s(-1)) of the elbow flexors on an isokinetic dynamometer, 15 females aged 22.0+/-2.0 years (mean +/- s) were allocated to a control group (no treatment, n = 7) or a cryotherapy group (n = 8). Subjects in the cryotherapy group immersed their exercised arm in cold water (15 degrees C) for 15 min immediately after eccentric exercise and then every 12 h for 15 min for a total of seven sessions. Muscle tenderness, plasma creatine kinase activity, relaxed elbow angle, isometric strength and swelling (upper arm circumference) were measured immediately before and for 3 days after eccentric exercise. Analysis of variance revealed significant (P < 0.05) main effects for time for all variables, with increases in muscle tenderness, creatine kinase activity and upper arm circumference, and decreases in isometric strength and relaxed elbow angle. There were significant interactions (P<0.05) of group x time for relaxed elbow angle and creatine kinase activity. Relaxed elbow angle was greater and creatine kinase activity lower for the cryotherapy group than the controls on days 2 and 3 following the eccentric exercise. We conclude that although cold water immersion may reduce muscle stiffness and the amount of post-exercise damage after strenuous eccentric activity, there appears to be no effect on the perception of tenderness and strength loss, which is characteristic after this form of activity.", "In this study, we investigated the effect of water immersion on physical test performance and perception of fatigue/recovery during a 4-day simulated soccer tournament. Twenty high-performance junior male soccer players (age 15.9 +/- 0.6 years) played four matches in 4 days and undertook either cold-water immersion (10 +/- 0.5 degrees C) or thermoneutral water immersion (34 +/- 0.5 degrees C) after each match. Physical performance tests (countermovement jump height, heart rate, and rating of perceived exertion after a standard 5-min run and 12 x 20-m repeated sprint test), intracellular proteins, and inflammatory markers were recorded approximately 90 min before each match and 22 h after the final match. Perceptual measures of recovery (physical, mental, leg soreness, and general fatigue) were recorded 22 h after each match. There were non-significant reductions in countermovement jump height (1.7-7.3%, P = 0.74, eta(2) = 0.34) and repeated sprint ability (1.0-2.1%, P = 0.41, eta(2) = 0.07) over the 4-day tournament with no differences between groups. Post-shuttle run rating of perceived exertion increased over the tournament in both groups (P < 0.001, eta(2) = 0.48), whereas the perceptions of leg soreness (P = 0.004, eta(2) = 0.30) and general fatigue (P = 0.007, eta(2) = 0.12) were lower in the cold-water immersion group than the thermoneutral immersion group over the tournament. Creatine kinase (P = 0.004, eta(2) = 0.26) and lactate dehydrogenase (P < 0.001, eta(2) = 0.40) concentrations increased in both groups but there were no changes over time for any inflammatory markers. These results suggest that immediate post-match cold-water immersion does not affect physical test performance or indices of muscle damage and inflammation but does reduce the perception of general fatigue and leg soreness between matches in tournaments.", "The purpose of this study was to investigate the separate effects of cooling during the acute (within 60 min post-exercise) or subacute (24-168 h post-exercise) phase on skeletal muscle after exercise. Twenty-eight male subjects [mean (SD) 23.8 (1.8) years] were randomly assigned to the control (COTG, n=10), cold-water immersion (CWIG, n=9), and double-cold-water immersion groups (DCWIG, n=9). The cold-water immersion (15 min) was administered to the subjects' legs after calf-raise exercise (CWIG: after recording initial post-exercise measures, DCWIG: after recording initial and 24 h post-exercise measures). Magnetic resonance T2-weighted images were obtained to calculate the T2 relaxation time (T2) of the triceps surae muscle before, immediately after, and at the following times post-exercise: 20, 40, and 60 min, and 24, 48, 96 and 168 h. In addition, the ankle joint range of motion, serum creatine kinase and lactate dehydrogenase, and muscle soreness level were investigated before and after exercise. In all groups, significant T2 elevations in the gastrocnemius muscle appeared from immediately after to 60 min after exercise (P<0.05). Thereafter, COTG showed significantly re-elevated T2 levels in the gastrocnemius at 96-168 h post-exercise (P<0.05), while CWIG and DCWIG showed significantly smaller T2 values than the COTG at 96 h post-exercise (P<0.05). In addition, COTG showed larger increases in serum enzymes at 96 h post-exercise (not significant) and significantly greater muscle soreness levels at 48 h post-exercise (P<0.05) than the cooling groups. The results of this study may suggest that cooling has no dramatic effect, but some minor effects on reducing exercise-induced muscle edema in the subacute phase and relieving the extent of the damaged muscle cells.", "To determine the efficacy of warm whirlpool, cold whirlpool, and contrast therapy in the treatment of delayed-onset muscle soreness.\n Subjects performed eccentric contractions of the elbow flexors and received 4 treatments: immediately postexercise and 24, 48, and 72 hours postexercise. Treatments consisted of 24-minute treatments with warm whirlpool, cold whirlpool, contrast therapy, or no treatment.\n Fifty-six sex-matched volunteers from the University of Pittsburgh.\n Measurements were taken at 5 assessment times: pre-exercise (0 hours); prior to treatment at 24, 48, and 72 hours postexercise; and at 96 hours postexercise. Dependent variables were degrees of resting elbow flexion, active elbow flexion, and extension; perceived soreness values on a Graphic Pain Rating Scale; and maximal voluntary isometric contraction. A repeated-measures analysis of variance (group by time) and Tukey post hoc analysis were used to determine which treatment groups differed significantly in returning subjects to pre-exercise values.\n Cold whirlpool and contrast therapy were found to return subjects to baseline values of resting elbow flexion and perceived soreness significantly more than warm whirlpool or no treatment (P < .01). Additionally, warm whirlpool was found to be more effective than no treatment in the return of resting elbow flexion (P < .01).\n These results suggest that cold whirlpool and contrast therapy are more effective than warm whirlpool or no treatment in alleviating delayed-onset muscle soreness in the elbow flexors." ]

[ "17182126", "17521544", "16531621", "16820564", "20947859", "10573067", "16877299", "15235901", "17659916" ]

[ "Feasibility and safety of granulocyte colony-stimulating factor treatment in patients with acute myocardial infarction.", "[Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function].", "Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial.", "Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial.", "AXIS: a trial of intravenous granulocyte colony-stimulating factor in acute ischemic stroke.", "Randomized, placebo-controlled, double-blind, multicenter trial of efficacy and safety of granulocyte colony-stimulating factor in liver transplant recipients.", "Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment.", "A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia.", "Usefulness of granulocyte colony-stimulating factor in patients with a large anterior wall acute myocardial infarction to prevent left ventricular remodeling (the rigenera study)." ]

[ "This study examined feasibility and safety of granulocyte colony-stimulating factor (G-CSF) treatment for patients with acute myocardial infarction (AMI).\n Forty patients with AMI related with the left anterior descending coronary artery, who underwent successful percutaneous coronary intervention (PCI), were randomized into G-CSF group (n=18) or Control group (n=22). G-CSF treatment was started within 24 h after PCI. 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) was performed at 4 days and 6 months after AMI. SPECT data was analyzed for LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF) and myocardial perfusion.\n LVEF at 6 months was significantly better than that at 4 days in G-CSF group (p=0.013), but not changed in Control group (p=0.245). Although no significant difference was observed for LVEDV between the two groups, LVESV tended to be decreased only in G-CSF group. In G-CSF group, defect score (DS) was significantly decreased from 4 days to 6 months after AMI. Restenosis rate at 6 months after AMI was not significantly different between the two groups.\n G-CSF treatment for patients with AMI was effective and did not have any clinical and angiographic adverse effects.", "It is difficult to distinguish the effects early revascularization and regenerative therapy have on left ventricular function in patients with acute myocardial infarction (AMI). This study was an investigation into three groups of patients who had a revascularized anterior wall AMI and depressed left ventricular function (i.e., ejection fraction < 45%). The aim was to compare changes in left ventricular function between patients who received regenerative therapy and those who did not.\n Patients were randomly assigned to receive either an intracoronary infusion of autologous mononuclear bone marrow cells (Group I; n=10) or systemic administration of granulocyte colony-stimulating factor (G-CSF) (Group II; n=10), or to a control group (Group III; n=10). In Group I, intracoronary infusion was carried out 7(2) days after AMI. Group-II patients received a 10-day course of subcutaneous G-CSF injections, 10 .g/kg per day starting 5 days after AMI. Ventricular function was assessed at baseline and 3-month follow-up.\n A 20% increase in mean ejection fraction was observed in Group I, compared with increases of 4% (P<.01) and 6% (P<.05) in Groups II and III, respectively.\n Intracoronary infusion of mononuclear bone marrow cells in patients with AMI and poor ventricular function was associated with better short-term functional recovery than previously reported. However, mobilization of stem cells by G-CSF did not have a significant influence on functional recovery.", "Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of subcutaneous G-CSF injections on left ventricular function in patients with ST-elevation myocardial infarction.\n Seventy-eight patients (62 men; average age, 56 years) with ST-elevation myocardial infarction were included after successful primary percutaneous coronary stent intervention <12 hours after symptom onset. Patients were randomized to double-blind treatment with G-CSF (10 microg/kg of body weight) or placebo for 6 days. The primary end point was change in systolic wall thickening from baseline to 6 months determined by cardiac magnetic resonance imaging (MRI). An independent core laboratory analyzed all MRI examinations. Systolic wall thickening improved 17% in the infarct area in the G-CSF group and 17% in the placebo group (P=1.0). Comparable results were found in infarct border and noninfarcted myocardium. Left ventricular ejection fraction improved similarly in the 2 groups measured by both MRI (8.5 versus 8.0; P=0.9) and echocardiography (5.7 versus 3.7; P=0.7). The risk of severe clinical adverse events was not increased by G-CSF. In addition, in-stent late lumen loss and target vessel revascularization rate in the follow-up period were similar in the 2 groups.\n Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group.", "The efficacy of intracoronary infusion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) has not been compared between patients with acute (AMI) versus old myocardial infarction (OMI). In addition, the potential risk of restenosis associated with G-CSF-based stem cell therapy has not been evaluated in the setting of drug eluting stent (DES) implantation.\n We randomly allocated 96 patients with myocardial infarction who underwent coronary revascularization with DES for the culprit lesion into 4 groups. Eighty-two patients completed 6-month follow-up; AMI cell infusion (n=25), AMI control (n=25), OMI cell infusion (n=16), and OMI control group (n=16). In cell infusion groups, PBSCs were mobilized by G-CSF for 3 days and delivered to infarcted myocardium via intracoronary infusion. The AMI cell infusion group showed a significant additive improvement in left ventricular ejection fraction (LVEF) and remodeling compared with controls (change of LVEF: +5.1+/-9.1% versus -0.2+/-8.6%, P<0.05; change of end-systolic volume: -5.4+/-17.0 mL versus 6.5+/-21.9 mL, P<0.05). In OMI patients, however, there was no significant change of LVEF and ventricular remodeling in spite of significant improvement of coronary flow reserve after cell infusion. G-CSF-based cell therapy did not aggravate neointimal growth with DES implantation.\n Intracoronary infusion of mobilized PBSCs with G-CSF improves LVEF and remodeling in patients with AMI but is less definite in patients with OMI. G-CSF-based stem cell therapy with DES implantation is both feasible and safe, eliminating any potential for restenosis.", "Granulocyte colony-stimulating factor (G-CSF) is a promising stroke drug candidate. The present phase IIa study assessed safety and tolerability over a broad dose range of G-CSF doses in acute ischemic stroke patients and explored outcome data.\n Four intravenous dose regimens (total cumulative doses of 30-180 μg/kg over the course of 3 days) of G-CSF were tested in 44 patients in a national, multicenter, randomized, placebo-controlled dose escalation study (NCT00132470; www.clinicaltrial.gov). Main inclusion criteria were a 12-hour time window after stroke onset, infarct localization to the middle cerebral artery territory, a baseline National Institutes of Health Stroke Scale range of 4 to 22, and presence of diffusion-weighted imaging/perfusion-weighted imaging mismatch.\n Concerning the primary safety end points, we observed no increase of thromboembolic events in the active treatment groups, and no increase in related serious adverse events. G-CSF led to expected increases in neutrophils and monocytes that resolved rapidly after end of treatment. We observed a clinically insignificant drug-related decrease of platelets. As expected from the low number of patients, we did not observe significant differences in clinical outcome in treatment vs. placebo. In exploratory analyses, we observed an interesting dose-dependent beneficial effect of treatment in patients with DWI lesions > 14-17 cm³.\n We conclude that G-CSF was well-tolerated even at high dosages in patients with acute ischemic stroke, and that a substantial increase in leukocytes appears not problematic in stroke patients. In addition, exploratory analyses suggest treatment effects in patients with larger baseline diffusion-weighted imaging lesions. The obtained data provide the basis for a second trial aimed to demonstrate safety and efficacy of G-CSF on clinical end points.", "Infection and rejection are two common complications after liver transplants. In a preliminary study, administration of granulocyte colony-stimulating factor (G-CSF) to liver transplant recipients was associated with a decrease in sepsis episodes, sepsis-related deaths, and rejection compared with a historical control group of patients. The purpose of this study was to evaluate further the efficacy of G-CSF in liver transplant patients in a randomized, placebo-controlled, double-blind, multicenter trial.\n Adult patients with a United Network Organ Sharing classification of 1 or 2 were randomized to receive a placebo, 100 microg/day of G-CSF or 300 microg/day of G-CSF. The study drug was started preoperatively and then continued after the transplant for a maximum of 21 days. Patients were evaluated for microbiologically-documented infection, biopsy-proven rejection, number of treatments for rejection, length of stay in the intensive care unit and hospital, graft survival, death, and adverse events.\n During the first 30 days after the transplant, the median peak white blood cell count was 16.5x10(9)/L, 34.6x10(9)L, and 54.8x10(9)/L for the placebo, low-dose G-CSF, and high-dose G-CSF patients, respectively. The incidence of infection was 30% in G-CSF patients (34 of 114 patients) and 34% in placebo patients (20 of 58 patients). Except for more nosocomial pneumonias in the G-CSF patients (7 in 114 patients vs. 0 in 58 patients, P=0.056), the types of infections and causative organisms were also similar in both treatment groups. Although the number of treatments for clinically suspected or proven rejection was similar in the G-CSF and placebo patients, biopsy-proven rejection occurred more often in G-CSF patients (34 of 114 patients or 30%) than placebo patients (11 of 58 patients or 19%) (P=0.093). There were no cases of graft loss caused by rejection. G-CSF had no effect on length of stay in the intensive-care unit or hospital. There were 22 G-CSF patients (18%) and 10 placebo patients (15%) who died within 120 days after the transplant. No serious adverse events were attributed to G-CSF.\n Despite producing substantial increases in the white blood cell count after the transplant, G-CSF had no beneficial effects on infection, rejection, or survival in this study. Biopsy-proven rejection and nosocomial pneumonias were more common in patients treated with G-CSF compared with those taking the placebo. No serious adverse events were attributed to G-CSF.", "D-Ala1-peptide T-amide (DAPTA) has shown neuroprotection in vitro against gp120-induced loss of dendritic arborization and is promulgated as a CCR5 antagonist. A multisite, randomized, double-blind clinical trial of DAPTA versus placebo prior to combination antiretroviral therapy conducted with human immunodeficiency virus (HIV)-1 seropositive participants having cognitive impairment showed no overall cognitive effect, though subgroups with greater impairment and CD4 cell counts of 201 to 500 cells/mm3 at baseline showed significant improvement. The objective of this study was to examine whether intranasal administration of DAPTA at a dose of 2 mg three times per day (tid) was associated with a reduction of cerebrospinal fluid (CSF) and peripheral (plasma and serum) viral load among a subgroup of participants completing 6 months of treatment. Baseline and 6-month CSF (n = 92) and peripheral (plasma n = 33; serum n = 24) viral load were measured by the Roche Ultrasensitive assay, version 1.5, with reflexive use of the AMPLICOR assay and preservation of the blind. A DAPTA treatment indicator variable was tested using generalized linear models on change in viral load. Peripheral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group. No group differences in CSF viral load were found. This retrospective study on a limited subgroup of the original trial sample indicated that DAPTA treatment may reduce peripheral viral load without concomitant CSF effects. Future studies should be undertaken to confirm the existence of this result and the CSF-periphery dissociation observed with respect to HIV-1-associated cognitive-motor impairment.", "Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear.\n We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC).\n Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups.\n The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required.", "Intracoronary injection of bone marrow stem cells seems to improve left ventricular (LV) function after acute myocardial infarction (AMI). Granulocyte colony-stimulating factor (G-CSF) could improve myocardial function and perfusion noninvasively through mobilization of stem cells into peripheral blood, although previous clinical trials have produced controversial results. Forty-one patients with large anterior wall AMI at high risk of unfavorable remodeling were randomized 1:2 to G-CSF (10 microg/kg/day for 5 days) or to conventional therapy. All patients underwent successful primary or rescue percutaneous coronary intervention. LV function was assessed by echocardiography before G-CSF administration, > or =5 days after AMI, and at follow-up. Only patients with a LV ejection fraction <50% at baseline were enrolled in the study. After a median follow-up of 5 months (range 4 to 6) patients treated with G-CSF exhibited improvement in LV ejection fraction, from 40 +/- 6% to 45 +/- 6% (p = 0.068) in the absence of LV dilation (LV end-diastolic volume from 147 +/- 33 to 144 +/- 46 ml at follow-up, p = 0.77). In contrast, patients treated conventionally exhibited significant LV dilation (LV end-diastolic volume from 141 +/- 35 to 168 +/- 41 ml, p = 0.002) in the absence of change in LV ejection fraction (from 38 +/- 6% to 38 +/- 8%, p = 0.95). However, when comparing patients treated with G-CSF with controls, variations in these parameters were significantly different at 2-way analysis of variance (p = 0.04 for LV end-diastolic volume, p = 0.02 for LV ejection fraction). In conclusion, G-CSF prevents unfavorable LV remodeling and improves LV function in patients with large anterior wall AMI and decreased LV ejection fraction after successful percutaneous coronary intervention." ]

[ "12971850", "17915147", "3535601", "91836", "352100", "8201703", "7760866", "3142949", "1102398" ]

[ "[Early intravenous thrombolysis with recombinant tissue plasminogen activator for acute cerebral infarction].", "[Randomized controlled clinical trial of a home care unit intervention to reduce readmission and death rates in patients discharged from hospital following admission for heart failure].", "Intravenous heparin for the prevention of stroke progression in acute partial stable stroke.", "Reduction in sudden deaths by a multifactorial intervention programme after acute myocardial infarction.", "A controlled clinical trial of streptokinase and heparin in the treatment of major pulmonary embolism.", "A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia.", "A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group.", "A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis.", "Early changes in coagulation following a paracetamol overdose and a controlled trial of fresh frozen plasma therapy." ]

[ "To evaluate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) and to explore the most suitable dosage of rt-PA in the early treatment of the Chinese patients with acute cerebral infarction (ACI).\n The patients who suited for the standard were divided into three groups. Group A received rt-PA at 0.9 mg/kg, group B received rt-PA at 0.7 mg/kg, and group C did not receive any thrombolytic therapy. In thrombolytic groups, rt-PA at 8 mg was injected intravenously in a bolus at first and then the rest was given over 60 minutes. The maximal dosage was 90 mg. The Chinese stroke scale (CSS) and Barthel Index (BI) were used to evaluate the recovery of neurological functions after rt-PA treatment for 24 hours and 90 days. The hemorrhagic rate and 30 days mortality rate were also analysed.\n In group A the CSS significant effective rate was 41.18 percent at 24 hours and 76.47 percent at 90 days after thrombolysis. At 90 days BI significant effective rate was 58.82 percent. At 30 days hemorrhagic rate was 8.82 percent and mortality rate was 5.88 percent. In group B, the CSS significant effective rate was 39.39 percent at 24 hours and 69.70 percent at 90 days. At 90 days, BI significant effective rate was 54.55 percent, and at 30 days, hemorrhagic rate was 9.09 percent and mortality rate was 9.09 percent. In group C, the CSS significant effective rate was 21.21 percent, at 24 hours and 30.30 percent at 90 days (P>0.05). At 90 days, BI was 21.21 percent the mortality rate was 9.09 percent. At 30 days the mortality rate was no significant difference within three groups At 90 days, significant effective rate was 73.13 percent vs. 30.30 percent in thrombolytic and control groups (P=0.001 7). The significant disability rate was 13.43 percent vs. 24.24 percent.\n For Chinese individuals, with ACI, rt-PA thrombolysis was effective and safe. The dosage of 0.9 mg/kg for foreign people also fitted for Chinese individuals.", "To determine the effectiveness of a primarily educational intervention in heart failure (HF) patients implemented in a home care unit.\n This randomized controlled clinical trial involved 279 HF patients who were discharged from a tertiary-care hospital between February 2001 and June 2002. Patients with dementia, terminal non-cardiac disease, or chronic obstructive pulmonary disease were excluded. Data collected included the cause of cardiac decompensation. A primarily educational intervention was implemented in the patient's home for up to 15 days after hospital discharge. Treatment was adjusted during the first week if necessary. The primary outcome measure was the 1-year cumulative incidence of readmission or death. Secondary measures were the incidence of readmission, mortality, and emergency department admission. Telephone interviews were carried out 3, 6 and 12 months after discharge, and clinical records were updated when necessary. Emergency department admission in the first 6 months was monitored.\n At 1-year follow-up, 62 of the 137 patients (45.3%) in the intervention group had been readmitted or died, compared with 75 of the 142 (52.8%) in the control group, (relative risk=0.86, P=.232). Among patients who suffered decompensation because failure to adhere to treatment, 16 of the 45 (35.6%) in the intervention group were readmitted or died, compared with 34 of the 56 (60.7%) control group patients (relative risk=0.59, P=.016).\n This intervention is feasible but, when applied indiscriminately to every discharged heart failure patient, the best that can be expected is only a modest reduction in readmission and death rates, which, in this study in particular, did not achieve statistical significance.", "In a double-blind, placebo-controlled trial, 225 patients with acute partial stable thrombotic stroke were randomly assigned to receive continuous intravenous heparin therapy or placebo for 7 days for the prevention of stroke progression or death. No statistically significant difference between the two groups was found in degree of neurologic change; incidence of stroke progression after 7 days; or functional activity level of survivors at 7 days, 3 months and at 1 year after treatment. Compared with controls, a statistically significant greater number of patients in the group receiving heparin died in the year after the stroke. These deaths occurred 3 to 12 months after the initial stroke and probably were not related to treatment. Results of this study do not support the use of intravenous heparin to treat patients who have had acute partial stroke.", "375 consecutive patients below 65 years who had an acute myocardial infarction (AMI) took part in a randomised rehabilitation and secondary prevention trial (part of a W.H.O.-coordinated project) designed to study the effects of a multifactorial intervention programme on morbidity, mortality, return to work, &c. After three years' follow-up the cumulative coronary mortality was significantly smaller in the intervention group than in the controls (18.6% versus 29.4%, p = 0.02). This difference was mainly due to a reduction of sudden deaths in the intervention group (5.8% versus 14.4%, p less than 0.01). The reduction was greatest during the first six months after AMI. 18.1% in the intervention group and 11.2% in the controls (p less than 0.10) presented with non-fatal reinfarctions. The number of patients with new Q-QS findings at the end of the three years was, however, almost the same in both groups. The results suggest that organised aftercare during the first six months after AMI with special emphasis on optimum medical control and health education contributes significantly to a reduction in the number of sudden deaths.", "Treatment with streptokinase or heparin was allocated randomly to 20 patients with major pulmonary embolism verified by angiography. In addition, 4 patients treated with streptokinase and 1 patient treated with heparin were included in the trial prior to the start of treatment. Streptokinase of heparin was given for 72 hours and pulmonary angiography was repeated. The angiographic evidence of thrombolysis was significantly greater (p less than 0.01) in the 14 patients treated with streptokinase than in the 11 treated with heparin. In the heparin group, 1 patient died from massive embolism 15 hours after the start of treatment. In another patient who died 4 weeks later from cerebral glibolastoma, persistent massive embolism contributed to the fatal outcome. In the streptokinase group, 1 patient with a metastatic pulmonary carcinoma died 3 weeks after the start of treatment from gangrene of both legs following thrombotic occlusion of the inferior vena cava. Bleeding was more common after treatment with streptokinase than with heparin, but was not a serious problem in any patient. It is concluded that patients with life-threatening pulmonary embolism should be offered the benefits of streptokinase.", "Despite the widespread use of intraarterial thrombolytic therapy for peripheral arterial occlusive disease, a randomized study comparing its efficacy with that of operative intervention has never been performed. This study evaluates the potential of intraarterial urokinase infusion to provide clinical benefits in patients with acute peripheral arterial occlusion.\n Patients with limb-threatening ischemia of less than 7 days' duration were randomly assigned to intraarterial catheter-directed urokinase therapy or operative intervention. Anatomic lesions unmasked by thrombolysis were treated with balloon dilation or operation. The primary end points of the study were limb salvage and survival.\n A total of 57 patients were randomized to the thrombolytic therapy group, and 57 patients were randomized to the operative therapy group. Thrombolytic therapy resulted in dissolution of the occluding thrombus in 40 (70%) patients. Although the cumulative limb salvage rate was similar in the two treatment groups (82% at 12 months), the cumulative survival rate was significantly improved in patients randomized to the thrombolysis group (84% vs 58% at 12 months, p = 0.01). The mortality differences seemed to be primarily attributable to an increased frequency of in-hospital cardiopulmonary complications in the operative treatment group (49% vs 16%, p = 0.001). The benefits of thrombolysis were achieved without significant differences in the duration of hospitalization (median 11 days) and with only modest increases in hospital cost in the thrombolytic treatment arm (median $15,672 vs $12,253, p = 0.02).\n Intraarterial thrombolytic therapy was associated with a reduction in the incidence of in-hospital cardiopulmonary complications and a corresponding increase in patient survival rates. These benefits were achieved without an appreciable increase in the duration of hospitalization and with only modest increases in hospital cost, suggesting that thrombolytic therapy may offer a safe and effective alternative to operation in the initial treatment of patients diagnosed with acute limb-threatening peripheral arterial occlusion.", "The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate.\n We performed a multicenter trial comparing six weeks of oral anticoagulant treatment with six months of such therapy in patients who had a first episode of venous thromboembolism. Anticoagulant therapy consisted of warfarin or dicumarol. Of the 902 patients enrolled, 5 were later excluded because they had congenital protein C deficiency; 443 were randomly assigned to receive six weeks of oral anticoagulant therapy with a targeted international normalized ratio (INR) of 2.0 to 2.85, and 454 were randomly assigned to receive six months of such therapy. The initial diagnoses were confirmed by means of venography in cases of deep-vein thromboses (n = 790) and with perfusion-ventilation scanning or angiography in cases of pulmonary embolism (n = 107); recurrences were confirmed in the same way.\n After two years of follow-up, there had been 123 recurrences of venous thromboembolism that met the diagnostic criteria, 80 in the six-week group (18.1 percent; 95 percent confidence interval, 14.5 to 21.6) and 43 in the six-month group (9.5 percent; 95 percent confidence interval, 6.8 to 12.2). The odds ratio for recurrence in the six-week group was 2.1 (95 percent confidence interval, 1.4 to 3.1). There was no difference in mortality or the rate of major hemorrhage between the six-week and six-month groups.\n Six months of prophylactic oral anticoagulation after a first episode of venous thromboembolism led to a lower recurrence rate than did treatment lasting for six weeks. The difference between the two groups occurred between 6 weeks and 6 months after the start of treatment, and the rates of recurrence remained nearly parallel for 1 1/2 years thereafter.", "We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained. Twelve patients with moderate and 22 with severe alcoholic hepatitis were randomized to 28 days of peripheral parenteral nutrition (PPN) or standard therapy (ST). In the moderate group, six were treated with each therapy. In the severe group, 10 were treated with PPN and 12 with ST. Routine liver tests, hepatocyte function (galactose elimination capacity), estimated hepatic blood flow (galactose clearance) and assessment of ascites and encephalopathy were performed at randomization and at 28 days. Groups were equally matched at randomization. In the moderate group PPN produced no improvement in morbidity (liver tests) and mortality (no deaths). In the severe group there were seven deaths (4 PPN, 3 ST). PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time, serum albumin and galactose elimination capacity. PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after randomization. We conclude that PPN compared to ST (1) provides no benefit in moderate alcoholic hepatitis, but (2) did more rapidly improve morbidity (liver tests) and probably liver function in severe alcoholic hepatitis; (3) PPN did not improve early mortality, and (4) it had no deleterious effect on encephalopathy or ascites.", "Early changes in coagulation were found in patients following a paracetamol overdose. Low levels of clotting factors II, V and VII were present within 24 hours of the overdose. As the levels of factor II correlated with plasma fibrinogen values at this time, it is possible that they were consumed in the process of intravascular coagulation, although this was not supported by the presence of raised titres of fibrin degradation products. The prothrombin time ratio was greater than 2-2 within 30 hours of ingestion of the overdose in all patients who eventually died, whereas it was less than this in those developing only moderate liver damage. The administration of fresh frozen plasma to patients did appear to reduce the maximum abnormality of the prothrombin time ratio, which was significantly less three days after the overdose in the group receiving fresh frozen plasma. However, the coagulation disturbance was of short duration, and the prothrombin time ratio had also returned to normal within one week of the overdose in the control patients, and the administration of fresh frozen plasma did not appear to reduce the morbidity or mortality in the treated patients." ]

[ "15465981", "12464464", "12442883", "16199834", "12684609", "15076013", "18562423", "15641867", "17113759" ]

[ "Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder.", "Amisulpride vs. risperidone in chronic schizophrenia: results of a 6-month double-blind study.", "A double-blind, randomised comparative trial of amisulpride versus olanzapine in the treatment of schizophrenia: short-term results at two months.", "Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia.", "Amisulpride versus risperidone in the treatment of schizophrenic patients: a double-blind pilot study in Taiwan.", "A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia.", "Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial.", "Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial.", "A double-blind randomised comparative trial of amisulpride versus olanzapine for 2 months in the treatment of subjects with schizophrenia and comorbid depression." ]

[ "Limited randomized, controlled trial data exist on possible differences between atypical antipsychotics in efficacy, overall tolerability, and important indices of health status. The authors compared the efficacy and tolerability of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.\n In this 6-week, multicenter, double-blind, parallel-design, flexible-dose trial, patients were randomly assigned to receive ziprasidone (N=136) or olanzapine (N=133). Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and Clinical Global Impression (CGI) severity scale scores; secondary measures were scores on the CGI improvement scale, Positive and Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia. Tolerability assessments included fasting lipid profiles, fasting glucose and insulin measurements, electrocardiography, and monitoring of vital signs and body weight.\n The overall mean daily doses were 129.9 mg (SD=27.3) for ziprasidone and 11.3 mg (SD=2.8) for olanzapine. Both antipsychotics were efficacious in improving symptoms and global illness severity. The two treatment groups did not differ significantly in primary or secondary efficacy measures at endpoint or in by-visit analysis. Both agents were well tolerated. Body weight, total cholesterol, triglycerides, and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone; all between-group comparisons of these variables were significant and favored ziprasidone. Olanzapine, but not ziprasidone, was associated with significant increases in fasting insulin level. No patient in either group exhibited a corrected QT interval >/=500 msec.\n During 6 weeks' treatment, ziprasidone and olanzapine demonstrated comparable antipsychotic efficacy. Differences favoring ziprasidone were observed in metabolic parameters.", "This multicenter, double-blind, randomized study evaluated the efficacy, safety and functional effects of two atypical antipsychotics, amisulpride and risperidone, in patients with chronic schizophrenia (DSM IV) with a recent worsening of symptoms. It was planned as a non-inferiority trial. 309 patients received amisulpride (400-1,000 mg/day) or risperidone (4-10 mg/day) for six months. Amisulpride was demonstrated to be not inferior to risperidone with respect to the decrease in Positive and Negative Syndrome Scale (PANSS) total score from baseline (90% 2-sided confidence interval (-5.6; 4.0)). Symptomatic improvement measured with the Brief Psychiatry Rating Scale (BPRS), the PANSS positive subscale, and the Bech Rafaelsen Melancholia Scale was similar in both groups. Amisulpride was significantly (p <.05) superior to risperidone in terms of response (>/=50% improvement in PANSS and BPRS total scores or \"very much/much improved\" on the Clinical Global Impression Scale) and also demonstrated better functional effects and subjective response. Both treatments were well tolerated and had a similar low incidence of extrapyramidal symptoms; however, amisulpride was associated with less weight gain and endocrine/sexual symptoms.", "To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia.\n A multinational, double-blind randomised clinical trial.\n Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride (200-800 mg/d) or olanzapine (5-20 mg/d).\n Short-term results were analysed after two months of treatment. The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale (BPRS). Other measures of efficacy and safety were also evaluated.\n Psychotic symptoms, as measured on the BPRS score, improved with both treatments, amisulpride being equivalent to olanzapine. All BPRS factor scores, as well as depressive symptoms, improved to a similar extent with both treatments. Less than five per cent of patients withdrew for adverse events, and there was no evidence for the emergence of extrapyramidal symptoms with either treatment. Statistically significant greater weight gain (2.7 +/- 3.9 kg) was observed during the study in the olanzapine group, compared with the amisulpride group (0.9 +/- 3.2 kg, p < 0.0001).\n Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia. Amisulpride offers a significant advantage in preserving body weight.", "The efficacy and safety of olanzapine were compared with those of ziprasidone.\n This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight.\n The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level.\n Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.", "The atypical antipsychotics, amisulpride and risperidone, have different receptor affinity characteristics. Although the relative efficacy of both drugs compared to conventional antipsychotics is well established, it remains unclear how the efficacy of amisulpride compares with risperidone. There have been no controlled studies comparing amisulpride to risperidone in Asian patients. The purpose of this study was to compare the efficacy and safety of amisulpride with that of risperidone in Taiwanese schizophrenic patients.\n Patients with productive positive symptoms (n = 48) were enrolled into this double-blind, randomized pilot study for 6 weeks. Patients received either amisulpride (400-800 mg/day) or risperidone (4-8 mg/day). Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), Social and Occupational Functioning Assessment Scale (SOFAS), and patients' subjective responses to treatment were assessed during the trial period. Adverse events were recorded at each follow-up visit.\n At the end of the trial, the mean dosage was 630 +/- 134 mg/day and 6.88 +/- 1.54 mg/day for amisulpride and risperidone, respectively. There was no significant difference in the reduction of the PANSS total score (amisulpride -24.1 versus risperidone -28.4, p = 0.999), the PANSS positive subscale score (amisulpride -6.8 versus risperidone -8.3, p = 0.467), the PANSS negative subscale score (amisulpride -5.6 versus risperidone -6.4, p = 0.999), or the CGI score between the two groups. The extrapyramidal symptom ratings, the improvement in the SOFAS (amisulpride 11.1 versus risperidone 10.0) and the subjective response (amisulpride 82% versus risperidone 83%) were comparable. No serious adverse events were recorded in either treatment group. There was a statistically significant body weight gain in the risperidone group. In contrast, there was a statistically, though not clinically, significant reduction of blood pressure and heart rate in the amisulpride group.\n This study suggests that amisulpride is as effective as risperidone in the treatment of patients with schizophrenia. Both drugs were well tolerated, but had different side effect profiles.", "Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, double-blind, randomized trial was performed to compare amisulpride and olanzapine in the treatment of acute schizophrenia. Adult schizophrenic patients with dominant positive symptomatology received amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. The primary efficacy variable was change from baseline of the Brief Psychiatric Rating Scale (BPRS) score, assessed with a non-inferiority analysis. The evolution of positive and negative symptomatology, depression, social functioning and quality of life were assessed. Safety evaluation included adverse event reporting, neurological status and body weight. The improvement of BPRS score was 32.7% in the amisulpride group and 33.0% in the olanzapine group; thus, the efficacy of amisulpride was not inferior to that of olanzapine. All other secondary efficacy outcome variables evolved to a similar extent in both groups. Adverse event frequency was similar in both groups. Amenorrhoea was encountered only in the amisulpride group (6.2% of patients), whereas elevations of liver transaminases were more frequent in the olanzapine group (17% versus 3.7% of patients). The incidence and mean extent of clinically relevant weight gain were higher in the olanzapine group (35.1% and 3.9 kg) than in the amisulpride group (20.6% and 1.6 kg). The efficacy of amisulpride is not inferior to that of olanzapine in the treatment of acute schizophrenia. The side-effect profile of the two drugs differed.", "Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.", "More head-to-head comparisons of antipsychotics are needed to discern the relative efficacy and safety profiles of these compounds. Thus, we compared ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder.\n Patients with DSM-III-R acute exacerbation of schizophrenia or schizoaffective disorder were randomly assigned to double-blind ziprasidone 40 to 80 mg b.i.d. (N = 149) or risperidone 3 to 5 mg b.i.d (N = 147) for 8 weeks. Primary efficacy measures included Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity of Illness scale (CGI-S) score; secondary measures included scores on the PANSS negative sub-scale, CGI-Improvement scale (CGI-I), and PANSS-derived Brief Psychiatric Rating Scale (BPRSd) total and core items. Safety assessments included movement disorder evaluations, laboratory tests, electrocardiography, vital signs, and body weight. Efficacy analyses employed a prospectively defined Evaluable Patients cohort. Treatment equivalence was conferred if the lower limit of the 95% confidence interval of the ziprasidone/risperidone ratio of least-squares mean change from baseline was > 0.60. Data were gathered from August 1995 to January 1997.\n Equivalence was demonstrated in PANSS total scores, CGI-S scores, PANSS negative subscale scores, BPRSd total and core item scores, and PANSS total and CGI-I responder rates. Both agents were well tolerated. Risperidone exhibited a significantly higher Movement Disorder Burden (MDB) score (p < .05) and higher incidences of prolactin elevation and clinically relevant weight gain. However, compared with current recommendations, study dosing may have been high for some risperidone-treated patients (mean dose = 7.4 mg/day) and low for some ziprasidone-treated patients (mean dose = 114.2 mg/day).\n Both agents equally improved psychotic symptoms, and both were generally well tolerated, with ziprasidone demonstrating a lower MDB score and less effect on prolactin and weight than risperidone.", "To compare the efficacy and safety of amisulpride and olanzapine in subjects with schizophrenia and comorbid depression in a randomised double-blind trial.\n Eighty-five adult patients fulfilling DSM-IV criteria for schizophrenia and presenting a depressive episode were randomised to amisulpride (200-600 mg/day) or olanzapine (5-15 mg/day) for 8 weeks. Primary efficacy variables were change in Calgary Depression Scale (CDS) score and Clinical Global Impression (CGI) of Change. Safety was monitored by adverse event reporting and determination of extrapyramidal function and metabolic variables.\n The mean change from baseline of CDS score was -6.84 in the amisulpride group and -7.36 in the olanzapine group. 65.9% and 61.5% of subjects, respectively, were considered \"much\" or \"very much\" improved. No significant inter-group difference in effect size was observed. The frequency of adverse events was low and emergence of extrapyramidal symptoms was not seen. Four patients in the olanzapine group developed abnormal triglyceride levels. Mean weight gain was 1.45 and 0.5 kg, respectively, in the olanzapine and amisulpride groups.\n Amisulpride and olanzapine are effective in patients with schizophrenia and comorbid depression. Tolerance of both drugs was acceptable, although use of olanzapine was associated with a trend toward greater metabolic side-effects ." ]

[ "15993304", "10323611", "10748957", "2381003", "11549952", "16881426", "6994679", "7673302", "1280145" ]

[ "Treatment of second degree facial burns with allografts--preliminary results.", "Management of partial thickness facial burns (comparison of topical antibiotics and bio-engineered skin substitutes).", "The role of alternative therapy in the management of partial thickness burns of the face--experience with the use of moist exposed burn ointment (MEBO) compared with silver sulphadiazine.", "Comparison of a hydrocolloid dressing and silver sulfadiazine cream in the outpatient management of second-degree burns.", "Evaluating the role of alternative therapy in burn wound management: randomized trial comparing moist exposed burn ointment with conventional methods in the management of patients with second-degree burns.", "Comparison of efficacy of 1% silver sulfadiazine and Acticoat for treatment of partial-thickness burn wounds.", "Safety and efficacy of a new synthetic burn dressing: a multicenter study.", "Wound healing in partial-thickness burn wounds treated with collagenase ointment versus silver sulfadiazine cream.", "European comparative clinical study of Inerpan: a new wound dressing in treatment of partial skin thickness burns." ]

[ "Facial burns are very common and have significant clinical impact. However, the treatment regimen for superficial to deep facial burns is not well defined. The purpose of this study was to investigate the effects of cadaver skin grafting in deep partial thickness facial burns in comparison to standard care. In a prospective open study design severely injured patients with superficial and deep partial thickness burns were randomized into the group receiving open treatment with silversulfadiazine (standard n=5) or into the group receiving early superficial debridement followed by coverage with glycerolized cadaver skin (n=5). The outcome measures were time and quality of wound healing, and incidence of hypertrophic scarring at 3 and 6 months post burn. There were no significant differences in demographics between groups. In the group treated with the allogenic material time to reepithelialization was 10.5 days, while it was 12.4 days in the silversulfadiazine group (p<0.05). Scar quality was found to be significantly improved in the allogenic treatment group. Three and 6 months postburn there were no patients with significant hypertrophic scarring in the allogenic group while there were two patients who developed hypertrophic scars in the silversulfadiazine group (p<0.05). In this study, we demonstrated that glyzerolized cadaver allograft skin represents a superior biological dressing for shallow and deep partial thickness facial burns. This is in concordance with other reports on scalds. It would be worthwhile to perform more clinical studies with a larger number of patients to further evaluate the effect and function of allogenic skin for facial burns.", "This study compared the effect of standard topical antibiotic management versus a biological skin substitute wound closure for mid-partial thickness burns of the face. Adult patients with mid-dermal facial burns produced by flash flames or flame exposure were studied using a randomized prospective study design. Total daily burn care time, pain (0-10 scale) and healing time were monitored. Immediately after partial thickness debridement, the entire face burn, including ears, was closed with a bioengineered skin substitute coated with fibronectin (TransCyte) or treated by the open technique using bacitracin ointment applied 2-3 times daily. 21 patients were studied, with 10 patients in the skin substitute group. We found a significant decrease in wound care time 0.35 +/- 0.1 versus 1.9 +/- 0.5 h, decrease in pain of 2 +/- 1 versus 4 +/- 2 and re-epithelialization time 7 +/- 2 versus 13 +/- 4 days in the skin substitute group compared to topical antibiotics. We can conclude that a bioengineered skin substitute significantly improves the management and healing rate of partial thickness facial burns, compared to the standard open topical ointment technique.", "Conventional management of partial thickness facial burn wounds includes the use of silver sulphadiazine dressings. Silver sulphadiazine forms an overlying slough that makes wound healing assessment difficult. Moist exposed burn ointment (MEBO) has been proposed as the ideal burn wound dressing both for burns of the face and other sites. Proponents of MEBO claim that it accelerates wound healing and results in scarless wound healing and at the same time reduce bacterial colonisation and the need for analgesics. We present here our experience with MEBO in the management of partial thickness burns of the face.\n One hundred and fifteen patients with partial thickness burns were randomly assigned to conventional treatment or MEBO. Out of this, 112 were analysed. Thirty-nine patients sustained facial burns; 17 received MEBO and 22 received silver sulphadiazine. Patients were followed up daily until the burn wounds were reduced by 75% of original body surface area (BSA).\n In patients with facial burns, MEBO was similar to silver sulphadiazine therapy with respect to rate of wound healing. Minimal slough was present over the wounds in MEBO-treated wounds resulting in clearer assessment of healing progression.\n Advantages of MEBO as compared to silver sulphadiazine in the management of partial thickness burns of the face include convenient change of dressing and easier assessment of healing progression. This suggests that MEBO is a useful alternative therapy for partial thickness burns of the face.", "The purpose of this prospective randomized study was to evaluate the use of an occlusive hydrocolloid dressing (Duoderm hydroactive, Squibb) and silver sulfadiazine (Silvadene, Marion) cream in the outpatient management of second-degree burns. The inclusion criteria consisted of burns less than 15% total body surface area that were evaluated within 24 hours of injury and did not require hospital admission. Fifty patients were randomly assigned after having been screened through a list of seven exclusion criteria. On initial evaluation the burns were photographed and screened for causative agent, location, size, depth, tetanus status, and presence of associated burns and injuries. Patients were seen in followup at least biweekly and evaluated for wound bed healing, wound margin healing, pain, number of dressing changes between visits, and ease of dressing application and removal. On final evaluation the burns were photographed and inspected for appearance of the healed burn, repigmentation, wound contraction, approximate time for dressing change, patient compliance, limitation of activity, overall impression of the treatment, and number of days for complete healing. Results were compared using a two-tailed t-test with p less than 0.01. Both groups were statistically similar in age, sex, and size. Duoderm-treated burns had statistically significantly better wound healing, repigmentation, less pain, fewer dressing changes, less time for dressing changes, and less cost. Duoderm-treated patients had statistically significantly less limitation of activity, better patient compliance, greater patient comfort, better overall acceptance, and felt the treatment was more aesthetically pleasing. The results reveal that the Duoderm Hydroactive dressings are superior to Silvadene cream in the outpatient management of second-degree burns.", "Moist exposed burn ointment (MEBO), from China, has been said to revolutionize burn management.\n Our study was conducted to compare MEBO with conventional management (C) with respect to the rate of wound healing, antibacterial and analgesic effect, and hospital costs.\n This is a prospective, randomized, controlled clinical trial conducted between 1 March 1997 and 24 October 1998.\n The trial was conducted in a specialized burn facility located in a tertiary referral hospital in a developed and industrialized island-state in Southeast Asia.\n We randomly assigned 115 consecutive patients between the ages of 12 and 80 who had partial-thickness thermal burns covering less than 40% of body surface area (BSA) to receive either MEBO or C. Fifty-seven patients were assigned to MEBO and 58 patients to C. The latter group received twice-daily dressing changes; MEBO patients received MEBO every 4 hours.\n Patients were hospitalized until 75% BSA had healed. BSA was determined by visual inspection and charted on Lund and Browder charts regularly. Wound healing rate, bacterial infection rate, pain score, and hospitalization costs were recorded.\n The median time to 75% healing was 17.0 and 20.0 days with MEBO and C, respectively (HR = 0.67, 95% CI = 0.41-1.11, P =.11), suggesting similar efficacy between the 2 modalities. Bacterial infection rates were similar between the 2 groups (HR = 1.10, 95% CI = 0.59-2.03, P =.76). MEBO imparted a greater analgesic effect in the first 5 days of therapy and reduced hospital costs by 8%.\n MEBO is as effective as conventional management but is not the panacea for all burn wounds. The use of MEBO eases the management of face and neck burns and facilitates early institution of occupational therapy in hand burns. It confers better pain relief such that fewer opiates are used during the first 5 days after burn injury.", "Acticoat (Smith & Nephew, Hull, UK) is a silver-coated dressing reported to reduce infection and exhibit antimicrobial activity in wounds.\n The purpose of the present study was to compare the efficacy ofacticoat and 1% silver sulfadiazine (1% AgSD) for treatment of partial thickness burn wounds.\n The authors reviewed 50 patients who had partial thickness burn wounds less than 25% admitted to Siriraj Burn Unit from May 2002 to September 2005. All patients were divided into 2 groups: the acticoat treated group (25 patients) and the 1% silver sulfadiazine treated group (25 patients). The 2 groups were compared for the etiology of burn wound, demographic data including age, sex, % Total Body Surface Area burn (TBSA%), cultured organisms, wound infection and outcome of Length Of hospital Stay (LOS) and level of pain.\n The authors found no significant differences in age, TBSA (%) between both groups. 7 patients (28%) developed wound infection. There were no differences in wound infection and LOS between both groups (p > 0.05). All of the patients who developed wound infection responded well to targeted topical and systemic antibiotic treatment. The 1% AgSD treated group (6 of 25, 24%) obtained more split thickness skin graft to close the granulation defects compared to patients who were treated with acticoat (4 of 25, 16%) but no statistical significance, p = 0.32). Average pain scores in the acticoat treated groups were significantly lower than the 1% AgSD treated group (4 +/- 0.6 versus 5 +/- 0.7, respectively).\n The present study confirms the efficacy of acticoat treatment in partial thickness burn wound. The authors conclude that acticoat has an advantage of limiting the frequency of replacement of the dressing and provides a less painful alternative to wound care with 1% AgSD with comparable incidence of burn wound infection. This is due to its long wear time and the ease of application and removal.", "A three-tiered, multicenter study evaluated the safety and efficacy of a new synthetic dressing for burn injuries. The first tier compared use of the test dressing with use of a conventional topical chemotherapeutic agent; the test dressing afforded greater patient comfort, equivalent control of bacterial growth, less frequent dressing change, and possibly faster reepithelialization. Drawbacks included difficulty of application, poor adherence during the first 24 hours after injury, frequent necessity to repair cracks and fissures, and inability to easily monitor burn wounds for bacterial growth. Subsequent tiers were noncomparative but included patients with more severe injuries. The test dressing may be useful in treating superficial and moderate second-degree burns of less than 20% of the total body surface area and possibly in treating iatrogenic \"burn\" wounds such as donor sites. Its use on third-degree burns is not recommended.", "During burn care the wounds must be repeatedly debrided of adherent and loose debris until the decision is made to surgically excise and graft the wound or to await epithelialization. Though native proteolytic enzymes in the skin or those produced by colonizing bacteria can speed eschar separation, the use of exogenous enzymes for wound debridement may accelerate wound cleaning and healing. Collagenase digests native and denatured collagen in necrotic tissue. This multicenter trial of 79 patients with partial-thickness wounds compared the efficacy of collagenase ointment applied with polymyxin B sulfate/bacitracin powder with the efficacy of standard topical antimicrobial therapy (control) in which silver sulfadiazine cream (1%) was used to debride paired burn sites. Patients selected for the study had two noncontiguous, partial-thickness, comparably sized, and anatomically similar burn wounds. Ages of patients ranged from 5 to 60 years (mean 33 years). The total body surface area burned ranged from 2% to 30% (mean 13.6%). Mean burn sizes used for study treatment were 366 cm2 (26 to 2310 cm2) for collagenase sites and 355 cm2 (26 to 2394 cm2) for control sites. Sites on each patient were randomly assigned to treatment with either collagenase or control. Endpoints were time to clean wound bed (absence of retained debris) and time to healing (complete epithelialization). The sites treated with collagenase cleaned in less time (mean 9.3 days) than the control sites (mean 11.6 days). Similarly the collagenase sites healed faster than the control sites (mean 19 vs 22.1 days).(ABSTRACT TRUNCATED AT 250 WORDS)", "Eleven European burns centres in five countries (Belgium, England, Germany, Italy, Switzerland) participated in a prospective, randomized clinical trial comparing a new wound dressing Inerpan with conventional dressings such as petroleum jelly gauze, petroleum jelly gauze with antibiotics and silver sulphadiazine cream. The indication was partial skin thickness burns and 62 patients were included. In each patient, two similar lesions (with respect to depth and surface area) were compared, one being treated with Inerpan, the other one with a control dressing. The following parameters were studied: healing time, quality of healing, intensity of pain, local tolerance and frequency of dressing changes. Analysis of the results showed that Inerpan-treated sites healed faster than conventional ones, and were associated with a highly significant reduction of pain. The frequency of dressing changes was greatly reduced and the local tolerance was good." ]

[ "11519503", "16531616", "18753638", "17982182", "19463379", "19427428", "12937308", "18946065", "16765759" ]

[ "Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.", "Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.", "Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke.", "Prasugrel versus clopidogrel in patients with acute coronary syndromes.", "Glycoprotein IIb/IIIa inhibitors improve outcome after coronary stenting in clopidogrel nonresponders: a prospective, randomized study.", "Clinical outcomes of patients with diabetic nephropathy randomized to clopidogrel plus aspirin versus aspirin alone (a post hoc analysis of the clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance [CHARISMA] trial).", "Randomized controlled trial of clopidogrel plus aspirin to prevent hemodialysis access graft thrombosis.", "Cardiovascular outcomes after a change in prescription policy for clopidogrel.", "Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial." ]

[ "Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients.\n We randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months.\n The first primary outcome--a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke--occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome--the first primary outcome or refractory ischemia--occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86; 95 percent confidence interval, 0.79 to 0.94; P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.2 percent [corrected] vs. 1.8 percent; P=0.13) or hemorrhagic strokes (0.1 percent vs. 0.1 percent).\n The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.", "Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events.\n We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes.\n The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046).\n In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.).\n Copyright 2006 Massachusetts Medical Society.", "Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel.\n In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned.\n A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).\n The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)\n 2008 Massachusetts Medical Society", "Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention.\n To compare prasugrel, a new thienopyridine, with clopidogrel, we randomly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel (a 60-mg loading dose and a 10-mg daily maintenance dose) or clopidogrel (a 300-mg loading dose and a 75-mg daily maintenance dose), for 6 to 15 months. The primary efficacy end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The key safety end point was major bleeding.\n The primary efficacy end point occurred in 12.1% of patients receiving clopidogrel and 9.9% of patients receiving prasugrel (hazard ratio for prasugrel vs. clopidogrel, 0.81; 95% confidence interval [CI], 0.73 to 0.90; P<0.001). We also found significant reductions in the prasugrel group in the rates of myocardial infarction (9.7% for clopidogrel vs. 7.4% for prasugrel; P<0.001), urgent target-vessel revascularization (3.7% vs. 2.5%; P<0.001), and stent thrombosis (2.4% vs. 1.1%; P<0.001). Major bleeding was observed in 2.4% of patients receiving prasugrel and in 1.8% of patients receiving clopidogrel (hazard ratio, 1.32; 95% CI, 1.03 to 1.68; P=0.03). Also greater in the prasugrel group was the rate of life-threatening bleeding (1.4% vs. 0.9%; P=0.01), including nonfatal bleeding (1.1% vs. 0.9%; hazard ratio, 1.25; P=0.23) and fatal bleeding (0.4% vs. 0.1%; P=0.002).\n In patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding. Overall mortality did not differ significantly between treatment groups. (ClinicalTrials.gov number, NCT00097591 [ClinicalTrials.gov].)\n Copyright 2007 Massachusetts Medical Society.", "The aim of this study was to assess, in clopidogrel nonresponders undergoing elective percutaneous coronary intervention (PCI), the benefit of adjusted antiplatelet therapy with glycoprotein (GP) IIb/IIIa antagonist administration during PCI for 1-month clinical outcome.\n Numerous biological studies have reported interindividual variability in platelet response to clopidogrel with clinical relevance, and high post-treatment platelet reactivity (adenosine diphosphate-induced aggregation >70%) has been proposed to define nonresponse to clopidogrel. These nonresponders might benefit from tailored antiplatelet therapy.\n One hundred forty-nine clopidogrel nonresponders referred for elective PCI were prospectively included and randomized to \"conventional group\" (n = 75) or \"active group\" with GP IIb/IIIa antagonist (n = 74). All patients received 250-mg aspirin and 600-mg clopidogrel before PCI and platelet testing.\n The rate of cardiovascular events at 1 month was significantly lower in the \"active group\" than in the \"conventional group\": 19% (n = 14) versus 40% (n = 30), p = 0.006, odds ratio: 2.8; 95% confidence interval: 1.4 to 6.0. No patient in either group had post-procedural Thrombolysis In Myocardial Infarction major bleeding or required transfusions.\n The present study suggested benefit of tailored antiplatelet therapy during elective PCI with GP IIb/IIIa antagonist for clopidogrel nonresponders without increased bleeding risk.", "No prospective randomized trial has specifically examined the long-term outcomes of clopidogrel use in patients with chronic kidney disease. This study aimed to determine the risks and benefits of long-term clopidogrel administration in patients with diabetic nephropathy, the most common form of chronic kidney disease. We performed a post hoc analysis of the CHARISMA trial, which randomly assigned patients without active acute coronary syndrome, but with established atherosclerotic disease (symptomatic) or multiple risk factors for atherosclerotic disease (asymptomatic), to clopidogrel plus aspirin versus placebo plus aspirin. All CHARISMA patients (n = 15,603) were separated into the 3 groups: nondiabetic patients, diabetic patients without nephropathy, and diabetic patients with nephropathy. Within each group, outcomes of patients randomly assigned to clopidogrel were compared with those of patients randomly assigned to placebo. Outcomes in the prespecified CHARISMA subgroups of asymptomatic and symptomatic patients were also compared with respect to study drug assignment and nephropathy status. Patients with nephropathy who received clopidogrel had no difference in bleeding, but experienced significantly increased cardiovascular (CV) and overall mortality compared with those randomly assigned to placebo. There were no differences in bleeding, overall mortality, or CV mortality for nondiabetic or diabetic patients without nephropathy who received clopidogrel versus placebo. In the asymptomatic cohort, patients with nephropathy randomly assigned to clopidogrel had significantly increased overall and CV mortality compared with placebo, whereas asymptomatic patients without nephropathy randomly assigned to clopidogrel had no significant mortality difference compared with placebo. In conclusion, this post hoc analysis suggested that clopidogrel may be harmful in patients with diabetic nephropathy. Additional studies are needed to investigate this possible interaction.", "Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden. Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis. The study was designed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis. The study was a randomized, double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers. Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were randomized to receive either double placebos or aspirin (325 mg) and clopidogrel (75 mg) daily. Participants were to be monitored while receiving study medications for a minimum of 2 yr. The study was stopped after randomization of 200 participants, as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy. The cumulative incidence of bleeding events was significantly greater for those participants, compared with participants receiving placebos [hazard ratio, 1.98; 95% confidence interval (CI), 1.19 to 3.28; P = 0.007]. Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event (P = 0.006). There was no significant benefit of active treatment in the prevention of thrombosis (hazard ratio, 0.81; 95% CI, 0.47 to 1.40; P = 0.45), although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis (hazard ratio, 0.52; 95% CI, 0.22 to 1.26; P = 0.14). In the hemodialysis population, therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis.", "Drug-reimbursement policies may have an adverse effect on patient outcomes if they interfere with timely access to efficacious medications for acute medical conditions. Clopidogrel in combination with aspirin is the recommended standard of care for patients receiving coronary stents to prevent thrombosis. We examined the population-level effect of a change by a Canadian provincial government in a pharmacy-benefits program from a prior-authorization policy to a less restrictive, limited-use policy on access to clopidogrel among patients undergoing percutaneous coronary intervention (PCI) with stenting after acute myocardial infarction.\n We conducted a population-based, retrospective, time-series analysis from April 1, 2000, to March 31, 2005, of all patients 65 years of age or older with acute myocardial infarction who underwent PCI with stenting in Ontario, Canada. The primary outcome was the composite rate of death, recurrent acute myocardial infarction, PCI, and coronary-artery bypass grafting at 1 year, with adjustment for sex and age. The secondary outcome was major bleeding.\n The rate of clopidogrel use within 30 days after hospital discharge following myocardial infarction increased from 35% in the prior-authorization period to 88% in the limited-use period. The median time to the first dispensing of a clopidogrel prescription decreased from 9 days in the first period to 0 days in the second period. The 1-year composite cardiovascular outcome significantly decreased from 15% in the prior-authorization group to 11% in the limited-use group (P=0.02). Rates of bleeding in the two groups did not change.\n The removal of a prior-authorization program led to improvement in timely access to clopidogrel for coronary stenting and improved cardiovascular outcomes.\n 2008 Massachusetts Medical Society", "Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long-term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events.\n Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0-3.0; n=3371) or clopidogrel (75 mg per day) plus aspirin (75-100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00243178.\n The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76; p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively).\n Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy." ]

[ "7951964", "9046143", "11601430", "11166969", "15089956", "16564618", "9311323", "8929263", "16078340" ]

[ "Effect of pronation and supination orthosis on Morton's neuroma and lower extremity function.", "Surgery of Morton's neuroma: dorsal or plantar approach?", "Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex.", "The effect of opioids on phantom limb pain and cortical reorganization.", "Evidence-based postoperative pain management in nursing: is a randomized-controlled trial the most appropriate design?", "A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury.", "Determining the effectiveness of a clinical-practice intervention in improving the control of pain in outpatients with cancer.", "Percutaneous radio-frequency neurotomy for chronic cervical zygapophyseal-joint pain.", "Efficacy of cognitive-behavioral intervention for juvenile primary fibromyalgia syndrome." ]

[ "Twenty-three adult patients with Morton's neuroma of one foot were randomized to receive in-shoe orthoses made from a hard, compressed, felt material that would either pronate or supinate both feet. The response of the neuroma pain was measured using subjective visual analogue scales, an objective examination, and the MACTAR patient-specific measure of maximal function. The development of any other lower limb symptoms was also recorded. The pain associated with Morton's neuroma was not significantly altered by changing the position of the foot with the compressed felt orthosis. Forcibly pronating the foot did not produce a significant incidence of lower limb symptoms in the short term.", "In this prospective study, 52 patients with 55 neuromas were studied in two groups. 26 patients underwent excision of the neuroma through a plantar approach and 26 through a dorsal approach. Average follow-up was 3.1 years after excision. Histology confirmed a neuroma in 51 cases. Results show that in the dorsal group weight-bearing and return to work was faster, and the duration of hospital stay was shorter, than in the plantar group. There were five painful scars in the plantar group and two in the dorsal group.", "The chronic electrical stimulation of a motor cortical area corresponding to a painful region of the body, by means of surgically-implanted epidural electrodes is a validated therapeutical strategy to control medication-resistant neurogenic pain. Repetitive transcranial magnetic stimulation (rTMS) permits to stimulate non-invasively and precisely the motor cortex. We applied a 20-min session of rTMS of the motor cortex at 10 Hz using a 'real' or a 'sham' coil in a series of 14 patients with intractable pain due to thalamic stroke or trigeminal neuropathy. We studied the effects of rTMS on pain level assessed on a 0-10 visual analogue scale from day 1 to day 12 following the rTMS session. A significant pain decrease was observed up to 8 days after the 'real' rTMS session. This study shows that a transient pain relief can be induced in patients suffering from chronic neurogenic pain during about the week that follows a 20-min session of 10 Hz-rTMS applied over the motor cortex.", "The efficacy of oral retarded morphine sulphate (MST) was tested against placebo in a double-blind crossover design in 12 patients with phantom limb pain after unilateral leg or arm amputation. Two counterbalanced treatment phases of 4 weeks each were initiated with an intravenous test infusion of MST or Placebo. The titration phase was 2 weeks. The dose of MST was titrated to at least 70 mg/day and at highest 300 mg/day. Pain intensity was assessed hourly on visual analog scales during a 4-week treatment-free phase, both treatment phases and at two follow-ups (6 and 12 months). Reorganization of somatosensory cortex, electric perception and pain thresholds as well as selective attention were measured pre- and post-treatment. A significant pain reduction was found during MST but not during placebo. A clinically relevant response to MST (pain reduction of more than 50%) was evident in 42%, a partial response (pain reduction of 25-50%) in 8% of the patients. Neuromagnetic source imaging of three patients showed initial evidence for reduced cortical reorganization under MST concurrent with the reduction in pain intensity. Perception and pain thresholds were not significantly altered whereas attention was significantly lower under MST. Thus, opioids show efficacy in the treatment of phantom limb pain and may potentially influence also cortical reorganization. These data need to be replicated in larger patient samples.", "There is an increasing drive to make nursing care evidence-based. High quality evidence from systematic reviews relevant to postoperative pain relief exists, yet pain after surgery remains poorly controlled for many patients. This study aimed to assess whether implementing evidence-based pain management improved postoperative pain outcomes. Pain on a 0-10 scale was the primary outcome and analgesic consumption a secondary outcome. A baseline audit was undertaken on four surgical wards to establish whether there was a need for the study. A randomized-controlled trial was then designed to assess the effects of implementing an evidence-based approach to postoperative pain management. The four wards were randomized to receive the intervention or act as a control. Outcomes were assessed 3 months after the intervention on both intervention and control wards. The intervention (implementation of an oral analgesic algorithm derived from systematic reviews) was then implemented on the control wards and outcomes reassessed after 3 months on the control wards. The intervention was designed using an evidence-based approach to effective implementation. Four interactive sessions covered: (1) detailed feedback of baseline data and discussion (utilizing audit and feedback), (2) why systematic reviews, analgesic league tables and choice of drugs to develop an analgesic algorithm (see Figure 1), (3) principles of evidence based health care (EBHC), including critical appraisal and (4) facilitation and change workshop. The findings revealed no significant differences in pain level or drug use between the intervention and control wards. However, the control wards also changed during the control period. Possible explanations for this are discussed. When looking at changes compared with baseline, both intervention and control wards increased their use of algorithm drugs and reduced use of non-algorithm drugs during the study. No effects were found on pain in the intervention wards. Pain ratings at rest since surgery, on movement since surgery and worst pain on movement were significantly reduced compared with baseline in the control wards. Although there are many pressures to utilize a randomized-controlled trial study design in the culture of evidence-based health care, there will be times, especially when implementing complex changes in practice that other types of design should be considered.", "Past evidence has shown that motor cortical stimulation with invasive and non-invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non-invasive brain stimulation--transcranial direct current stimulation (tDCS)--on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity.", "To determine the effectiveness of a clinical-practice intervention in improving the control of pain in outpatients with cancer.\n Between July 5 and September 30, 1995, a randomized, controlled trial of 510 cancer outpatients and 13 oncologists was conducted at 23 clinics in Indiana. All the patients completed assessments of their pain, their pain regimens, and the degrees of relief received; they were surveyed again by mail four weeks after their clinic visits. The intervention group's clinical charts contained a summary of the completed pain scales; the oncologists who treated these patients were instructed to review the summary sheet prior to an evaluation. This summary was not available for the oncologists treating the patients in the control group. Each patient's pain management index (PMI) was calculated: the patient's pain medication level was rated on a scale of 0 to 3; the patients's pain level was rated on a scale of 0 to 3 and then subtracted from the first rating. A negative PMI was interpreted as representing insufficient treatment. Data were analyzed with several statistical tests.\n In all, only 320 patients who reported cancer-related pain were used in the analysis: 160 to 260 in the control group and 160 of 250 in the intervention group. The groups were similar with respect to demographics, cancer sites, and performance status. A significant difference (p = .0162) in the physicians' prescription patterns was found. In the control group, prescriptions for 86% of the patients did not change, with no decrease in analgesic prescriptions; for 14% of the patients analgesic prescriptions increased. In the intervention group, analgesic prescriptions changed for 25% of the patients, decreasing for 5% and increasing for 20%. A decrease in the incidence of pain described as more than life's usual aches and pains was found for the intervention group (p = .05). No significant difference was found between the groups for the patients undertreated for pain, as measured by PMIs.\n Although analgesic regimens were altered significantly when the physicians understood more about the patient's pain, cancer pain management remains a complex problem. Future studies should focus on the long-term systematic incorporation of simple pain-assessment tools into daily outpatient oncology practices as well as on innovative ways to address other aspects of managing cancer pain.", "Chronic pain in the cervical zygapohyseal joints is a common problem after whiplash injury, but treatment is difficult. Percutaneous radiofrequency neurotomy can relieve the pain by denaturing the nerves innervating the painful joint, but the efficacy of this treatment has not been established.\n In a randomized, double-blind trial, we compared percutaneous radio-frequency neurotomy in which multiple lesions were made and the temperature of the electrode making the lesions was raised to 80 degrees C with a control treatment using an identical procedure except that the radio-frequency current was not turned on. We studied 24 patients (9 men and 15 women; mean age, 43 years) who had pain in one or more cervical zygapophyseal joints after an automobile accident (median duration of pain, 34 months). The source of their pain had been identified with the use of double-blind, placebo-controlled local anesthesia. Twelve patients received each treatment. The patients were followed by telephone interviews and clinic visits until they reported that their pain had returned to 50 percent of the preoperative level.\n The median time that elapsed before the pain returned to at least 50 percent of the preoperative level was 263 days in the active-treatment group and 8 days in the control group (P=0.04). At 27 weeks, seven patients in the active-treatment group and one patient in the control group were free of pain. Five patients in the active-treatment group had numbness in the territory of the treated nerves, but none considered it troubling.\n In patients with chronic cervical zygapophyseal-joint pain confirmed with double-blind, placebo-controlled local anesthesia, percutaneous radio-frequency neurotomy with multiple lesions of target nerves can provide lasting relief.", "There are currently no controlled studies of behavioral interventions for juvenile primary fibromyalgia syndrome (JPFM). In this small-sample randomized study, we tested the efficacy of a behavioral intervention, i.e., coping skills training (CST), for the treatment of adolescents with JPFM. Outcomes tested in this study were functional disability, pain intensity, pain-coping efficacy, and depressive symptoms.\n Thirty patients with JPFM were randomly assigned to 8 weeks of either CST or self-monitoring. Adolescents in the CST condition received training in active pain-coping techniques, while those in the self-monitoring condition monitored daily pain intensity and sleep quality with no instructions about behavior change. After posttreatment assessment, subjects were crossed over into the opposite treatment arm for 8 weeks (so that all adolescents eventually received both CST and self-monitoring) and were reassessed at Week 16.\n At Week 8, adolescents in both conditions showed significant decrease in depressive symptoms and functional disability. Those who received CST showed significantly greater ability to cope with pain than those in the self-monitoring condition and a trend toward decreased pain intensity. At Week 16, adolescents had significantly lower levels of disability and depressive symptoms compared to baseline, but those who received self-monitoring followed by CST seemed to receive the most benefit.\n CST can lead to improved functioning among JPFM patients. Although some of the improvement may be due to increased monitoring and attention, CST provides the specific benefit of improving adolescents' ability to cope with pain." ]

[ "3114506", "10432161", "15574620", "12357146", "3899020", "14553868", "20063224", "7893564", "9743925" ]

[ "Prospective study of replacing administration sets for intravenous therapy at 48- vs 72-hour intervals. 72 hours is safe and cost-effective.", "A randomized trial of 72- versus 24-hour intravenous tubing set changes in newborns receiving lipid therapy.", "Randomized, controlled trial of slow versus rapid feeding volume advancement in preterm infants.", "Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery.", "Prevention of intraventricular haemorrhage by fresh frozen plasma.", "Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial.", "A randomized trial of increased intravenous hydration in labor when oral fluid is unrestricted.", "The effect of intravenous fluid infusion on blood and urine parameters of hydration and on state of consciousness in terminal cancer patients.", "A randomized trial of heparin and saline for maintaining intravenous locks in neonates." ]

[ "We prospectively studied the safety of replacing intravenous delivery systems, including those used in total parenteral nutrition, at 72- compared with 48-hour intervals in 487 patients. Although the prevalence of contamination of intravenous fluid was higher in administration sets replaced at 72-hour intervals (10/664, 1.5%) than in sets replaced every 48 hours (6/710, 0.8%), the difference is not statistically significant. Contamination in both groups was almost exclusively with small numbers of coagulase-negative staphylococci (range, 1 to 27 colony-forming units/mL); no contaminated infusion was associated with clinical signs of sepsis or concordant bacteremia. Contaminants were recovered less frequently from peripheral venous infusions (0.6%) than from infusions used for central venous access or hemodynamic monitoring (1.5%) or total parenteral nutrition (3.6%); infusions in an intensive care unit were more frequently contaminated (2.5%) than infusions on medical and surgical wards (0.9%). These data indicate that extrinsic contamination of intravenous fluid is a rare cause of endemic nosocomial septicemia, and for most infusions it is unnecessary to routinely replace delivery systems more frequently than every 72 hours.", "To compare the microbial contamination rate of infusate in the intravenous tubing of newborns receiving lipid therapy, replacing the intravenous delivery system at 72-hour versus 24-hour intervals.\n Infants requiring intravenous lipid therapy were randomly assigned to have intravenous sets changed on a 72- or a 24-hour schedule, in a 3:1 ratio, in order to compare the infusate contamination rates in an equivalent number of tubing sets.\n A 35-bed, teaching, referral, neonatal intensive-care unit (NICU).\n All neonates admitted to the NICU for whom intravenous lipid was ordered.\n Patients were randomized in pharmacy, on receipt of the order for intravenous lipid therapy, to either 72- or 24-hour administration set changes, and followed until 1 week after discontinuation of lipids or discharge from the NICU. Microbial contamination of the infusate was assessed in both groups at the time of administration set changes. Contamination rates were analyzed separately for the lipid and amino acid-glucose tubing sets. Patient charts were reviewed for clinical and epidemiological data, including birth weight, gestational age, gender, age at start of lipid therapy, duration of parenteral nutrition, and type of intravenous access.\n During the study period, 1,101 and 1,112 sets were sampled in the 72- and 24-hour groups, respectively. Microbial contamination rates were higher in the 72-hour group than the 24-hour group for lipid infusions (39/1,101 [3.54%] vs 15/1,112 [1.35%]; P=.001) and for amino acid infusions (12/1,093 [1.10%] vs 4/1,103 [0.36%]; P=.076). Logistic regression analysis controlling for birth weight, gestational age, and type of venous access showed that only the tubing change interval was significantly associated with lipid set contaminations (odds ratio, 2.69; P=.0013). The rate of blood cultures ordered was higher in the 72- versus the 24-hour group (6.11 vs 4.99 per 100 patient days of total parenteral nutrition; P=.017), and a higher proportion of infants randomized to the 72-hour group died (8% vs 4%; P=.05), although the excess deaths could not clearly be attributed to bacteremia.\n Microbial contamination of infusion sets is significantly more frequent with 72- than with 24-hour set changes in neonates receiving lipid solutions. This may be associated with an increased mortality rate.", "To determine whether infants who are fed initially and advanced at 30 mL/kg per day (intervention) take fewer days to get to full feedings than those who are fed initially and advanced at 20 mL/kg per day (control), without increasing their incidence of feeding complications and necrotizing enterocolitis (NEC). We also examined whether these infants regain birth weight earlier, have fewer days of intravenous fluids, and a have shorter hospital stay.\n A randomized, controlled, single-center trial was conducted in a Neonatal Intensive Care Unit of a community-based county hospital in Houston, Texas. Infants between 1000 and 2000 g at birth, gestational age < or =35 weeks, and weight appropriate for gestational age were allocated randomly to feedings of expressed human milk or Enfamil formula starting and advanced at either 30 mL/kg per day or 20 mL/kg per day. Infants remained in the study until discharge or development of stage > or =IIA NEC.\n A total of 155 infants were enrolled: 72 infants in the intervention group and 83 in the control group. Infants in the intervention group achieved full-volume feedings sooner (7 vs 10 days, median), regained birth weight faster (11 vs 13 days, median), and had fewer days of intravenous fluids (6 vs 8 days, median). Three infants in the intervention group and 2 control infants developed NEC for an overall incidence of 3.2% (relative risk: 1.73; 95% confidence interval: 0.30-10.06).\n Among infants between 1000 and 2000 g at birth, starting and advancing feedings at 30 mL/kg per day seems to be a safe practice and results in fewer days to reach full-volume feedings than using 20 mL/kg per day. This intervention also leads to faster weight gain and fewer days of intravenous fluids.", "Intraoperative hypovolemia is common and is a potential cause of organ dysfunction, increased postoperative morbidity, length of hospital stay, and death. The objective of this prospective, randomized study was to assess the effect of goal-directed intraoperative fluid administration on length of postoperative hospital stay.\n One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were randomly assigned to a control group (n = 50) that received standard intraoperative care or to a protocol group (n = 50) that, in addition, received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume. Length of postoperative hospital stay and postoperative surgical morbidity were assessed.\n Groups were similar with respect to demographics, surgical procedures, and baseline hemodynamic variables. The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group. Patients in the protocol group had a shorter duration of hospital stay compared with the control group: 5 +/- 3 versus 7 +/- 3 days (mean +/- SD), with a median of 6 versus 7 days, respectively ( = 0.03). These patients also tolerated oral intake of solid food earlier than the control group: 3 +/- 0.5 versus 4.7 +/- 0.5 days (mean +/- SD), with a median of 3 versus 5 days, respectively ( = 0.01).\n Goal-directed intraoperative fluid administration results in earlier return to bowel function, lower incidence of postoperative nausea and vomiting, and decrease in length of postoperative hospital stay.", "Seventy three preterm infants weighing less than 1500 g or less than 32 weeks' gestation, or both, were allocated randomly to treatment (fresh frozen plasma 10 ml/kg on admission and at 24 hours of age) or control groups. Fifteen (41%) out of 37 control patients sustained intraventricular haemorrhage compared with five (14%) of 36 patients receiving treatment (X2 = 5.24, P = 0.022). No difference was found in coagulation factors measured at birth or at 48 hours of age in both groups. Fresh frozen plasma appears to have a beneficial effect in the prevention of intraventricular haemorrhage.", "Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia.\n In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days.\n Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] =1.23; 95% confidence interval [CI]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (HR = 1.16; 95% CI: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms.\n The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes.", "Increased intravenous (IV) hydration is associated with decreased labor duration and oxytocin augmentation in nulliparous women when oral fluid is restricted. The objective of this study was to determine the effect of increased IV hydration on the duration of labor when access to oral fluid was unrestricted.\n Term, nulliparous women with uncomplicated singleton pregnancies were randomly assigned to receive lactated ringers at 250 ml per hour (IV fluid group) throughout active labor or usual care. All women were allowed unrestricted access to oral fluids.\n Eighty women completed the study, 37 in the IV fluid group and 43 in the usual care group. There was no difference in the primary outcome of total duration of labor (9.5 versus 9.4 hours) or in the secondary outcomes of duration of the first stage (7.9 versus 8.0 hours), duration of second stage (1.6 versus 1.4 hours), or rate of oxytocin augmentation (51% versus 44%).\n Increased IV hydration does not decrease labor duration in nulliparous women when access to oral fluid is unrestricted.", "This prospective study was undertaken to assess the state of hydration in terminal cancer patients with and without intravenous fluids during the last 48 hours of their lives and to correlate various measures of hydration with their state of consciousness. We examined indicators of hydration in the plasma and urine of 68 consecutive patients for whom data were available at 48 hours or less before death. Thirteen of the patients were being treated with intravenous (IV) fluids. Nearly all of the patients studied were found to be dehydrated, as determined by laboratory measurements. State of consciousness correlated inversely with serum sodium (p < 0.001) and urine osmolality (p < 0.02). Patients receiving intravenous fluids were not better hydrated than those without IV therapy, nor was their state of consciousness improved. In light of these findings, which suggest there is no clinical benefit from intravenous infusions, decisions regarding intravenous fluid therapy during the last hours of life should be guided by the preferences of the dying patient and his family.", "To determine the effects of saline, heparin 2 units (U) per ml saline, and heparin 10 U/ml saline flush solutions on the duration of intravenous (i.v.) locks and the incidence of i.v. infiltration in neonates.\n Randomized double-blind experiment.\n Tertiary-care nursery.\n Neonates (N = 90) hospitalized at birth in the intensive, intermediate care, or newborn units.\n Total hours from the time the i.v. was inserted to the time the i.v. was removed; hours from the time the i.v. was first flushed to the time the i.v. was removed; number of i.vs. removed because of infiltration.\n No statistical or clinical differences between the three groups for duration of i.v. nor for incidence of complications.\n The use of heparin in i.v. lock flush solution did not affect the duration of i.v. locks nor the incidence of infiltration in neonates." ]

[ "8285749", "6109989", "1468386", "9389261", "10545551", "8951252", "9462190", "7669374", "10771973" ]

[ "Randomised trial of routine versus selective paralysis during ventilation for neonatal respiratory distress syndrome.", "Pancuronium during mechanical ventilation speeds recovery of lungs of infants with hyaline membrane disease.", "Effect of morphine and pancuronium on the stress response in ventilated preterm infants.", "Comparison of suxamethonium and different combinations of rocuronium and mivacurium for rapid tracheal intubation in children.", "Randomized trial of permissive hypercapnia in preterm infants.", "The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.", "Randomised trial of volume controlled versus time cycled, pressure limited ventilation in preterm infants with respiratory distress syndrome.", "Morphine increases synchronous ventilation in preterm infants.", "Respiratory and systemic effects of inhaled dexamethasone on ventilator dependant preterm infants at risk for bronchopulmonary dysplasia." ]

[ "The strategy of non-selective neuromuscular paralysis was compared with that of synchronised (fast rate) ventilation and selective paralysis in infants receiving mechanical ventilation for respiratory distress syndrome with chronic lung disease as the primary outcome measure. One hundred and ninety three infants weighing under 2000 g were randomly allocated to receive either pancuronium during mechanical ventilation in the acute phase of respiratory distress syndrome (non-selective group) or synchronised ventilation (initial ventilatory rate at or above that of the infant's) (selective group). Infants in the selective group received pancuronium if they were consistently expiring during the inspiratory phase of the ventilator cycle. There was no significant difference between the groups with respect to birth weight, gestation, and sex distribution. There was no significant difference between the group with respect to death (selective 19%, non-selective 16%), pneumothorax (selective 14%, non-selective 14%), chronic lung disease (selective 49%), non-selective 47%), and oxygen dependency at 36 weeks' postmenstrual age (selective 32%, non-selective 39%). Routine paralysis of ventilated infants has potential complications that may be avoided by using synchronised ventilation. As the latter is not associated with an increased incidence of long term respiratory complications, it is concluded that it is the optimum strategy of the two for ventilating infants with respiratory distress syndrome.", "Spontaneous breathing during mechanical ventilation in newborn infants may damage the lung. To find out whether the prevalence of lesions which might be due to trauma was reduced by muscle relaxation, fifty infants who required mechanical ventilation of hyaline membrane disease were randomly assigned to treated and control groups. The treated infants were kept muscle relaxed with pancuronium bromide until they needed a FiO2 of 0.40 or less during ventilation. The mean birthweight, gestational age, age at entry to the trial, duration of intubation and ventilation, FiO2 during the acute phase of the illness, and ventilator pressures were closely comparable in the two groups. Two of twenty-six treated infants and one of twenty-four controls died. Four treated and five control infants acquired pneumothoraces and/or interstitial emphysema. The length of time that the treated infants required added oxygen was significantly less than in the control infants. All treated infants were breathing room air spontaneously by one month of age whereas seven control infants were still dependent on added oxygen, needing an average FiO2 of 0.35 to achieve a mean PaO2 of 6.5 kPa (49 mm Hg). These seven infants required added oxygen until they were 5-18 (mean 10) weeks old. Muscle relaxation during mechanical ventilation for hyaline membrane disease speeds recovery of the lungs, probably owing to a reduction in traumatic damage.", "Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.", "The use of suxamethonium in children is associated with undesirable side effects. The synergistic effect of a rocuronium-mivacurium combination can be considered as an acceptable alternative to suxamethonium in clinical practice. The calculated ED50 of the rocuronium-mivacurium mixture was only 62% of the predicted value assuming a purely additive interaction. The use of this combination has not been evaluated in children. In this two-part study, we assessed the intubating conditions and pharmacodynamics of suxamethonium, rocuronium, mivacurium or a rocuronium-mivacurium combinations in children. We studied 120 ASA I children of both sexes, aged 3-10 yr. Children were premedicated with trimeprazine 2 mg kg-1 orally, and received fentanyl 2 micrograms kg-1 and propofol 2 mg kg-1 for induction of anaesthesia. They were allocated randomly to receive one of the following drugs or drug combinations: suxamethonium 1.0 mg kg-1, mivacurium 0.2 mg kg-1, rocuronium 0.6 or 0.9 mg kg-1, mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 or mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1. In part 1, 60 s after administration of the neuromuscular blocking drug or drug combination, tracheal intubation was performed in 60 children by mimicking rapid sequence induction, and intubating conditions were evaluated by a blinded investigator according to a standard score. In part 2, neuromuscular monitoring was established before administration of neuromuscular blocking agent(s) and the time from injection of drug or drug combination until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded in another 60 children. The frequency of distribution of excellent or good intubating conditions in the higher dose of rocuronium and the combination groups were similar to those in the suxamethonium group, but significantly different (P < 0.05) from those in the mivacurium group. Mean onset time was faster in the suxamethonium (55.1 (SD 11.4) s), rocuronium 0.9 mg kg-1 (70.5 (37.7) s), mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 (67 (35.9) s) and mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1 (55 (26.7) s) groups compared with the mivacurium 0.2 mg kg-1 (116 (26.8) s) and rocuronium 0.6 mg kg-1 (97.9 (29) s) groups. This study demonstrated that the combination of rocuronium 0.45 mg kg-1 and mivacurium 0.15 mg kg-1 could possibly be considered as an acceptable alternative to suxamethonium when rapid sequence induction of anaesthesia is indicated in children because it provides uniform excellent intubating conditions and complete neuromuscular block in < 60 s.", "To determine whether a ventilatory strategy of permissive hypercapnia (PHC) reduces the duration of assisted ventilation in surfactant-treated neonates weighing 601 to 1250 g at birth.\n Forty-nine surfactant-treated preterm infants (birth weight: 854 +/- 163 g; gestational age: 26 +/- 1.4 weeks) receiving assisted ventilation were randomized during the first 24 hours of age to a PHC group (PaCO(2): 45-55 mm Hg) or to a normocapnia group (NC; PaCO(2): 35-45 mm Hg). The primary outcome measure was the total number of days on assisted ventilation. Uniform extubation and reintubation criteria were used for both groups. All patients received aminophylline before extubation.\n The total number of days on assisted ventilation expressed as median (25th-75th percentiles) was 2.5 (1.5-11.5) in the PHC group and 9.5 (2.0-22.5) in the NC group (Mann-Whitney U test). The number of patients on assisted ventilation throughout the first 96 hours after randomization was lower in the PHC group (log rank test). During that period, the ventilated patients in the PHC group had a higher PaCO(2) and lower peak inspiratory pressure, mean airway pressure, and ventilator rate than did those in the NC group. The percentage of patients requiring reintubation within 24 hours postextubation (PHC 17% vs NC 28%) and supplemental oxygen at 28 days of life (PHC 43% vs NC 64%) and the total days of oxygen supplementation (PHC 15 [4-53] vs NC 32 [17-50]) did not differ between the groups. There were no differences in mortality, air leaks, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or patent ductus arteriosus.\n A ventilatory strategy of PHC in preterm infants who receive assisted ventilation is feasible, seems safe, and may reduce the duration of assisted ventilation. assisted ventilation, respiratory distress syndrome, gentle ventilation, lung injury.", "To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support.\n A prospective randomized clinical trial.\n Three community-based level III neonatal intensive care units.\n A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50.\n Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit.\n No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants.\n When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.", "Fifty preterm infants weighing 1200 g or more with clinical and radiographic evidence of respiratory distress syndrome, requiring both mechanical ventilation and exogenous surfactant replacement, were randomly allocated to receive either volume controlled ventilation or time cycled, pressure limited ventilation. Tidal volume delivery in each group was deliberately controlled at 5-8 ml/kg so that the only difference between the two groups was the ventilatory modality, the manner in which tidal volume was delivered. The rest of the ventilatory management and clinical care was done according to protocol. The two modes of ventilation were compared by determining the time required to achieve pre-determined success criteria, based on either the alveolar-arterial oxygen gradient or the mean airway pressure as a standard against which the speed of weaning could be objectively assessed. Infants randomised to volume controlled ventilation met success criteria sooner and had a shorter duration of mechanical ventilation. These babies also had a significantly lower incidence of intraventricular haemorrhages and abnormal periventricular echodensities on ultrasound scans. Volume controlled ventilation seems to be both safe and effective in this group of patients.", "To examine the short-term cardiorespiratory effects of intravenous morphine infusion in ventilated preterm infants.\n A randomized double-blind placebo-controlled trial in a neonatal intensive care unit. Twenty-six preterm infants (29-36 weeks gestation) with hyaline membrane disease requiring ventilatory assistance on the first day after birth were included in the study. A loading dose of morphine 100 micrograms/kg over 30 min followed by a continuous intravenous infusion at 10 micrograms/kg per hour was given. Primary measures were heart rate, blood pressure, respiratory rate and interaction of spontaneous respiration with mechanical ventilation. Secondary measures were durations of oxygen therapy, ventilator therapy and hospitalization as well as incidence of bronchopulmonary dysplasia, periventricular haemorrhage and pneumothorax.\n Morphine-treated infants spent a significantly greater percentage of total ventilated time breathing in synchrony with their ventilators (median [IQ] = 72[58-87] vs 31[17-51]%; P = 0.0008). Heart rate and respiratory rate, but not blood pressure, were reduced in morphine-treated infants. Duration of oxygen therapy was reduced (median [IQ] = 4.5[3-7] vs 8[4.75-12.5] days; P = 0.046).\n Intravenous morphine infusion increases synchronicity of spontaneous and ventilator-delivered breaths in preterm infants. Morphine reduces heart rate and respiratory rate without reducing blood pressure, and may help to reduce duration of oxygen therapy in preterm infants with hyaline membrane disease.", "Short-term inhaled dexamethasone therapy was evaluated in a double blind placebo controlled trial in 36 ventilator dependent preterm neonates (BW < 1500 gm, postnatal age > 7 days) who were at risk for bronchopulmonary dysplasia. Pulmonary and systemic effects were compared at early (day 3), late (7-10 days) and post (14 days after initiation) phases of therapy. Airflow mechanics improved as demonstrated by a net 101% improvement in pulmonary resistance (a decrease from 139 to 101 cm H2O/L/s in the dexamethasone treated infants as compared to an increase from 153 to 267 cmH2O/L/s in the placebo treated infants during the early phase of therapy); this was associated with a 45% increase in inspiratory airflow (1.29 +/- 0.43 to 1.87 +/- 0.978 L/min; p < 0.01), and 37% increase in expiratory airflow. These changes resulted in a significant reduction in the work of breathing such that the mean tidal driving pressure significantly decreased from 13.6 cmH2O to 9.4 cm H2O with inhaled steroid administration. Though the brief duration of therapy did not result in cessation of ventilatory support, the level of support was significantly reduced (decreased values of oxygen supplementation, mean airway pressure and oxygenation index and increased ventilatory efficiency index). The inhaled dexamethasone therapy was also associated with systemic absorption of the drug as evidenced by transient but apparently reversible reduction in serum cortisol levels. No systemic side effects of hypertension, hyperglycemia or nosocomial sepsis were observed. These data demonstrate beneficial effects of short-term inhaled dexamethasone on the resistive airflow properties of preterm infants at risk for BPD and may provide adjunctive means to facilitate weaning in the ventilator dependent neonates." ]

[ "11205200", "10885603", "9440756", "1354275", "11955734", "7013971", "10437612", "7845115", "2196107" ]

[ "Optimum duration of oral adjuvant chemotherapy of HCFU for colorectal cancer; review of 5-year follow-up.", "The Scottish and Manchester randomised trial of neo-adjuvant chemotherapy for advanced cervical cancer.", "Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer.", "Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma.", "A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients.", "A randomized comparison of radiotherapy with a radiotherapy--chemotherapy combination in stage IV carcinoma of the head and neck.", "Prospective randomised trial on adjuvant hepatic-artery infusion chemotherapy after R0 resection of colorectal liver metastases.", "Long-term results of single course of adjuvant intraportal chemotherapy for colorectal cancer. Swiss Group for Clinical Cancer Research (SAKK)", "A randomized study comparing two regimens of neoadjuvant and adjuvant chemotherapy in multimodal therapy for locally advanced head and neck cancer." ]

[ "To investigate the optimal duration of oral HCFU administration for minimization of side effects induced by long-term administration.\n In total, 155 patients allocated to two groups of different duration of the therapy were reviewed: twice or three times per day doses of oral HCFU (8 mg/Kg body weight/day) for 3 months vs. 12 months.\n Though statistically significant difference was not found in cumulative survival and disease-free rates between the groups due to so many violations of duration of therapy, when reanalyzing the variables in order of real duration of therapy, those rates were significantly higher in patients treated for 300 and more days than less than 300 days (g-Wilcoxon test: p < 0.04). No significant difference was observed in the background factors between the groups.\n At least 300 days is suggested to be necessary to obtain the optimal effectiveness of adjuvant chemotherapy for curatively resected colorectal cancer.", "204 eligible patients were entered into a multicentre randomised trial of neo-adjuvant chemotherapy prior to radical radiotherapy. The aim of this study was to assess whether there was any survival advantage in patients undergoing chemotherapy and radiotherapy compared with those given radiotherapy alone. Patients were aged up to 70 years, performance status 0-1/2, with bulky stage IIb, stage III or stage IVa squamous or adenosquamous carcinoma. Three cycles of methotrexate 100 mg/m2 and cisplatin 50 mg/m2 were given at 2-weekly intervals before radical radiotherapy. 104 eligible patients received the combination treatment and 100 radiotherapy only. The two arms of the study were well balanced for tumour and patient characteristics. The response rate to chemotherapy was 49%, 33% of patients in the radiotherapy (XRT) alone arm and 45% of the combination arm were clinically free of tumour at the end of treatment. The median follow-up for surviving patients is 5.4 years (range: 11 months-8 years) and 84% have been followed-up for more than 4 years. 134 patients have died (68 XRT only, 66 combined arm). The median survival RT alone was 111 weeks (95% confidence interval (CI) 72-151 weeks), combination arm 125 weeks (95% CI 79-170 weeks). The estimated death ratio is 0.79 (P = 0.19, 95% CI 0.56-1.12). The estimated 3-year survival is 40% (95% CI 30-50%) RT only compared with 47% (95% CI 37-57%) in the combination arm. Acute and late toxicity of radiotherapy was not increased by the addition of chemotherapy.", "This study had two major goals: (1) to assess the effectiveness of a regimen of fluorouracil (5-FU) plus levamisole plus leucovorin as postoperative surgical adjuvant therapy for patients with high-risk colon cancer, and (2) to evaluate 6 months versus 12 months of chemotherapy.\n Patients with poor-prognosis stage II or III colon cancer were randomly assigned to receive adjuvant chemotherapy with either intensive-course 5-FU and leucovorin combined with levamisole, or a standard regimen of 5-FU plus levamisole. Patients were also randomly assigned to receive either 12 months or 6 months of chemotherapy, which resulted in four treatment groups.\n Eight hundred ninety-one of 915 patients entered (97.4%) were eligible. The median follow-up duration is 5.1 years for patients still alive. There was a difference among the four treatment groups with respect to patient survival, and a significant duration-by-regimen interaction was observed. Specifically, standard 5-FU plus levamisole was inferior to 5-FU plus leucovorin plus levamisole when treatment was given for 6 months (5-year survival rate, 60% v 70%; P < .01).\n There was no significant improvement in patient survival when chemotherapy was given for 12 months compared with 6 months. When chemotherapy was given for 6 months, standard 5-FU plus levamisole was associated with inferior patient survival compared with intensive-course 5-FU plus leucovorin plus levamisole. These data suggest that 5-FU plus levamisole for 6 months should not be used in clinical practice, whereas 6 months of treatment with 5-FU plus leucovorin plus levamisole is effective.", "About half the patients treated with curative resection for colorectal cancer do not survive long-term. Adjuvant chemotherapy given during and after surgery may prevent hepatic metastases and improve patient survival. In patients with colorectal cancer, we have done a multicentre, randomised controlled trial comparing five-year survival after intraportal infusion of fluorouracil (1 g per day) plus heparin (10,000 U per day) (130 patients) or heparin alone (123) during curative resection and for 7 days thereafter, or after resection alone (145). There was no reduction in liver metastasis or increased overall survival advantage in either active-treatment arm of the study. However, patients who had stage III, Dukes' C (lymph-node-positive) tumours resected and were treated with fluorouracil plus heparin had a significant (p less than 0.03) survival advantage of about 16% compared with surgery-only controls. Further study of intraportal infusion of chemotherapeutic agent as adjuvant treatment to surgery in patients with colorectal cancer appears worthwhile.", "To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC.\n Between November 1994 and March 1999, 157 patients with Stage IV, M(0) (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35-40 fractions, 1.8-2.0 Gy/fraction/day, 5 days/week, to a total dose 70-72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m(2) cisplatin, 2,200 mg/m(2) 5-fluorouracil, and 120 mg/m(2) leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis.\n With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 (p value = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (>or= Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (>or= Grade 3).\n We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival.", "Between 1975 and 1978, 23 patients with Stage IV, unresectable, squamous cell carcinoma of the head and neck were randomized to receive radiotherapy (RT, 11 patients), or radiotherapy-chemotherapy (RT & CT, 12 patients). The response rate for the 12 RT & CT patients was four complete remissions (CR) and four partial remissions (PR); the 11 RT patients had one CR and three PR. The presence of a responses (CR or PR) significantly enhanced the median survival (14 vs. 5 months; P = 0.005). The duration of objectives remission was longer among the RT & CT patients when compared with RT patients (6 vs. 2.3 months, P = 0.18). The median survival of the RT & CT group was 12 months compared with 5.6 months for the RT group (P = 0.13). One RT & CT patient remains alive with disease at 44 months, one RT patient remains alive without disease at 30 months. The present chemotherapy regimen did not modify the pattern of failure and only marginally increased patient survival. It did, however, increase the response rate. The authors plan to reactivate the trial with modification in the induction chemotherapy and the addition of postradiation maintenance CT consisting of sequential bleomycin and cis-platinum.", "The liver represents the predominant site of cancer relapse after curative resection of hepatic metastases from colorectal carcinoma. Adjuvant intra-arterial chemotherapy was therefore considered a promising therapeutic approach in high-risk patients.\n From July 1984 to December 1985, a total of 42 consecutive patients underwent R0 resection of colorectal liver metastases. Thirty patients with mesenteric lymph-node metastases (Dukes C) were randomised into two groups. In 14 group-A patients, a hepatic artery port catheter was placed during liver resection. Four courses of adjuvant chemotherapy were administered at 4-week intervals, consisting of mitomycin C (8 mg/m2, day 1) and 5-fluorouracil (800 mg/m2, days 1-5). Sixteen group-B patients served as controls. The 12 patients with no mesenteric lymph-node metastases (Dukes A/B) were included in the follow-up program.\n After 5 years, 64% of Dukes A/B patients and 29% of Dukes C patients were alive (P<0.01). The probability of remaining free of recurrent disease after 5 years and 10 years was 55% and 18%, respectively (P<0.01). No significant difference in either 5-year survival (25% vs 31%) or long-term disease-free status (15% vs 23%) was detected between groups A and B. The initial tumour relapse was shifted towards extrahepatic sites in group-A patients, but no difference was obtained regarding the definite distribution of recurrent disease.\n Routine application of adjuvant regional chemotherapy after R0 liver resection is not warranted.", "The efficacy of adjuvant chemotherapy after surgery for colorectal cancer remains unproven. We have investigated the efficacy of a perioperative intraportal cytotoxic regimen in a randomised trial of 533 patients with operable colorectal carcinoma. Patients were randomly assigned either a single course of portal infusion with mitomycin (10 mg/m2, one dose) plus fluorouracil (500 mg/m2 per 24 h for 7 days) starting immediately after surgery, or no adjuvant treatment. 505 (94%) were evaluable. At median follow-up of 8 years, adjuvant therapy reduced the risk of recurrence by 21% (hazard ratio 0.79 [95% CI 0.62-1.00], p = 0.051) and the risk of death by 26% (0.74 [0.57-0.97], p = 0.026). The lower risk of relapse was observed in all subgroups based on node status or localisation of the tumour; the risk reduction was greatest in patients with tumour-involved lymph nodes (Dukes' C; 0.67 [0.45-0.99], p = 0.045) and for those with colon cancer (0.78 [0.56-1.09], p = 0.151). Most of the difference in overall and disease-free survival could be attributed to a consistent reduction of all kinds of tumour recurrences (local relapses, liver metastases, and other distant metastases) in the treated group, rather than to a reduction of liver relapses only. We conclude that part of the benefit obtained with a single course of adjuvant chemotherapy via the portal vein for patients with operable colorectal carcinoma might be due to the systemic effects of the portal chemotherapy.", "Two regimens of neoadjuvant chemotherapy for previously untreated patients with locally advanced head and neck cancer were compared with the goal of identifying a regimen with a greater than 50% complete response (CR) rate. Patients with a performance status of 0 to 2 and normal end-organ function were randomized to receive either four cycles of neoadjuvant methotrexate, cisplatin, and continuous infusion 5-fluorouracil (5-FU) (MPF) (arm A), or four cycles of bleomycin, cisplatin, and methotrexate (PBM) alternating with cisplatin and 5-FU (PF) (arm B). Patients with a performance status of greater than 2 or a carbon monoxide diffusion capacity of less than 50% of the predicted value were assigned to the arm A regimen but were analyzed separately (arm C). Local therapy consisted of surgery (for patients with resectable disease) or radiation therapy followed by two cycles of adjuvant chemotherapy with the regimen that was administered initially. Of the 42 patients who were evaluated, 16 were randomized to arm A, 13 to arm B, and 13 to arm C. The clinical CR rate was 19% on arm A (95% confidence interval, 0% to 38%), 39% on arm B (95% confidence interval, 12% to 66%) (P = 0.41), and 54% on arm C (95% confidence interval, 27% to 81%). At a median follow-up time of 35 months, the 2-year actuarial survival rate was 61% on arm A, 69% on arm B (the P value was not significant), and 38% on arm C. The 2-year survival rate for all 42 patients who were treated was 57% and the median survival time was 31 months. Toxicities of neoadjuvant chemotherapy on all arms consisted of mild to moderate myelosuppression and renal toxicity. The incidence of moderate to severe mucositis was significantly higher on arm A than arm B (P = 0.02). Two cycles of adjuvant chemotherapy were administered to only 11 of 42 patients due to patient refusal or cumulative toxicity. In conclusion, both neoadjuvant chemotherapy regimens resulted in similar response and survival rates, but mucositis was more severe with arm A. However, since neither regimen was likely to cause a CR rate of greater than 50%, this study was closed to further patient accrual." ]

[ "15485728", "1913409", "15904750", "11812810", "8050255", "9243440", "10408998", "16461871", "15006907" ]

[ "Telephone reminders are effective in recruiting nonresponding patients to randomized controlled trials.", "Use of reminders for preventive procedures in family medicine.", "Can just-in-time, evidence-based \"reminders\" improve pain management among home health care nurses and their patients?", "Telephone reminders are a cost effective way to improve responses in postal health surveys.", "Patient-specific reminder letters and pediatric well-child-care show rates.", "A randomized trial of the impact of telephone and recorded delivery reminders on the response rate to research questionnaires.", "Effect of mailed reminders on the response rate in surveys among patients in general practice.", "Effect of telephone reminder/recall on adolescent immunization and preventive visits: results from a randomized clinical trial.", "A large population-based randomized controlled trial to increase attendance at screening for cervical cancer." ]

[ "Studies investigating means of recruiting participants to randomized controlled trials (RCTs) are sparse. We investigated the effects of telephone reminders as a recruitment strategy.\n Sick-listed employees received a written invitation to participate in a study comparing standard treatments with a solution-focused follow-up and were randomly allocated to an intervention or control group (n=703). Those who did not respond within 2 weeks received either 'no reminder' (n=242) or 'attempted telephone reminder' (n=256). Outcome was enrollment to the RCT.\n An intention to recruit analysis revealed no significant differences between the groups (P=.229). An intention to phone analysis among nonresponders revealed significant differences between 'no reminder' (recruited 4.5%) and 'attempted telephone reminder' (recruited 12.1%) (P=.003, odds ratio 2.89, 95% confidence interval [CI] 1.42-5.90). An analysis of numbers needed to phone showed that to recruit one more person in this group of nonresponders, we needed to phone 13 persons (95% CI=8-33).\n Systematic use of telephone calls can increase the recruitment rate among nonresponders in RCTs.", "To compare the effectiveness of three computerized reminder systems in the delivery of five preventive procedures in family practice.\n Prospective, randomized, controlled study.\n Ottawa Civic Hospital Family Medicine Centre.\n Of 8502 patients 15 years of age or more who were not in a hospital or institution 5883 were randomly assigned, by family, to a control group, a physician reminder group (passive) or a telephone or letter reminder group (active). The remaining 2619 patients were not included in the randomized portion of the study but were monitored.\n During 1 year the patients in the active reminder groups received a telephone call or letter reminding them of any overdue preventive procedures; for those in the passive reminder group the physician was reminded at an office visit to provide any overdue service.\n Rates of completion of the preventive procedures required.\n All three reminder systems significantly improved the delivery of preventive services (p less than 0.001). The procedure completion rates were 42.0% in the letter reminder group, 42.0% in the telephone reminder group, 33.7% in the physician reminder group and 14.1% in the randomized control group. The use of a letter was more cost-effective than the telephone system, but the physician reminder system was the most cost-effective.\n Computerized reminder systems do improve the delivery of preventive services in family practice.", "The purpose of this randomized, controlled, home care intervention was to test the effectiveness of two nurse-targeted, e-mail-based interventions to increase home care nurses' adherence to pain assessment and management guidelines, and to improve patient outcomes. Nurses from a large urban non-profit home care organization were assigned to usual care or one of two interventions upon identification of an eligible cancer patient with pain. The basic intervention consisted of a patient-specific, one-time e-mail reminder highlighting six pain-specific clinical recommendations. The augmented intervention supplemented the initial e-mail reminder with provider prompts, patient education material, and clinical nurse specialist outreach. Over 300 nurses were randomized and outcomes of 673 of their patients were reviewed. Data collection involved clinical record abstraction of nurse care practices and patient interviews completed approximately 45 days after start of care. The intervention had limited effect on nurse-documented care practices but patient outcomes were positively influenced. Patients in the augmented group improved significantly over the control group in ratings of pain intensity at its worst, whereas patients in the basic group had better ratings of pain intensity on average. Other outcomes measures were also positively influenced but did not reach statistical significance. Our findings suggest that although reminders have some role in improving cancer pain management, a more intensive approach is needed for a generalized nursing workforce with limited recent exposure to state-of-the-art pain management practices.", "To assess the effectiveness of a telephone reminder in increasing responses to postal surveys and to calculate the differential costs per completed questionnaire.\n Randomised controlled trial.\n Australian university and rehabilitation medicine practice.\n The trial was conducted in 1999 among the 143 non-respondents to a questionnaire about work related neck and upper body disorders. The questionnaire was sent to two Australian female samples: 200 office workers (Sample A) and 92 former rehabilitation medicine patients (Sample B). A reminder letter, another copy of the questionnaire and a final letter were sent at two week intervals. Half of the non-respondents within each sample were randomly selected to receive a telephone reminder just after the second mailout of the questionnaire. All direct costs were calculated.\n Responses were significantly higher among those who received the telephone reminder intervention (relative risk 2.54, 95% confidence intervals 1.43 to 4.52). Analysed by intention to phone, 47% of non-respondents in Sample A and 38% in Sample B returned a complete questionnaire after the intervention, compared with 21% and 10%, respectively, in the control groups. For the 112 women (combined samples) who returned completed questionnaires before randomisation, the average cost per respondent was AUD14. There was a higher total cost for the intervention groups (AUD851 versus AUD386 for controls), but the significantly higher number of additional completed responses (31 versus 12) resulted in a 15% lower marginal cost per completed questionnaire in those groups.\n Telephone reminders are cost effective in improving responses to postal surveys.", "The objective of this study was to determine whether patient-specific letters, which describe the content of an upcoming well-child appointment, improve the show rate of well-child appointments better than postcard reminders. In this prospective clinical trial conducted at a pediatric continuity clinic in a teaching hospital, 288 newborns were randomized to a letter, postcard, or control group. For every well-child appointment, families were sent either a letter pertaining to the particular well-child appointment or a postcard; the control group received no reminders. There were no differences in demographics among the groups. The show rates between the letter and postcard groups were not different, but were significantly higher than the show rate for the control group (75.0%, 73.7%, and 67.5%, respectively; P < .05). A cost comparison between the use of postcards versus not using postcards revealed a benefit in the former. We concluded postcard reminders are effective in improving show rates for well-child-care visits, and that patient-specific letters have no additional benefit above that of postcard reminders.", "A range of factors have been shown to affect the response rate to mailed questionnaires, but particular strategies to improve patients' response in trials conducted in general practice require further study.\n Non-responders in a larger trial were randomized to receive a telephone or recorded delivery reminder on the third contact. The cost of administration of each method was estimated.\n Significantly more patients returned completed questionnaires when sent questionnaires by recorded delivery, although the cost per patient contacted was nearly three times more than for contact by telephone.\n Our study indicates that sending reminders by recorded delivery, although more expensive, is more effective than telephone reminders for recruiting patients to a study in general practice using research questionnaires.", "Randomized trials were performed in Denmark and The Netherlands to determine the effect of mailed reminders on the response rate in surveys among patients in general practice. In both countries, general practitioners handed out questionnaires to 200 adult patients who came to visit them. An intervention group of 100 patients received reminders at 3 weeks after the visit, whereas a control group of the remaining 100 patients did not receive reminders. The response rate was significantly higher in the intervention groups than in the control group in The Netherlands (86% versus 55%, respectively) but not in Denmark (87% versus 81%, respectively). Mailed reminders can improve the response rate in surveys related to a general practice, but they are not effective in all situations.", "To measure the effect of telephone-based reminder/recall on immunization and well-child care (WCC) visit rates among adolescents in urban practices.\n Randomized clinical trial of telephone-based reminder/recall over 18 months.\n Four urban primary care practices.\n Adolescents aged 11 to 14 years.Intervention Adolescents within practices were randomized to study (n = 1496) or control groups (n = 1510). The study group was sent audiotaped telephone reminders about a scheduled or needed immunization or WCC visit. Households were called weekly if there was no response; telephone numbers were updated weekly. Controls received standard care.\n Baseline demographics and immunization and WCC visit rates were similar for study and control groups. The intervention was largely ineffective in improving immunization or WCC visit rates. Although at the end of the study, the study group had slightly higher hepatitis B coverage (3 vaccinations) (62% vs 57.8%; P = .02), WCC visits were the same (53% and 54%), and impact on other vaccinations was minimal. The effect of reminder/recall was equivalent across demographic subgroups (e.g., age, race/ethnicity, insurance). The major factor limiting intervention effectiveness was inaccurate telephone numbers. Seventy-one percent of study subjects with single telephone numbers throughout the study had a WCC visit vs 25% of study subjects with multiple/changed telephone numbers and 54% of controls (P<.001).\n An intensive telephone reminder and recall system was only minimally successful in improving immunization and WCC visit rates among urban adolescents. Lack of success was largely owing to changed or inaccurate telephone numbers.", "Although cervical cancer is one of the potentially most preventable malignancies, it is still fairly common. In settings with established screening programs, increased compliance is important for future reduction in cervical cancer incidence, but it is presently unclear how this can be effectively achieved.\n We conducted a randomized controlled trial including all 12,240 women invited to organized screening in Sweden. To increase compliance, three successive interventions were tested: (a) modified invitation versus the standard invitation letter, (b) reminder letter to nonattenders after the first intervention versus no reminder letter, and (c) phone reminder to nonattenders after the reminder letter versus no phone reminder. We analyzed the proportion of women attending screening after each intervention and the cumulative proportion after the interventions as well as the cumulative proportions of cytologic abnormalities.\n The modified invitation did not increase attendance compared with the standard invitation letter [difference 1.3% 95% confidence interval (CI) -0.3 to 2.9]. In contrast, a reminder letter increased the proportion of women attending with 9.2% (95% CI 7.9-10.5) compared with women who did not receive a reminder letter, and a phone reminder increased the proportion of women attending with 31.4% (95% CI 26.9-35.9). Combinations of modified invitation, written reminder, and phone reminder almost doubled attendance within 12 months, and the number of detected cytologic abnormalities was more than tripled.\n Simple reminders by mail and phone can drastically increase women's participation in Papanicolaou smear screening and increase the number of detected precursor lesions and thereby save lives." ]

[ "16340187", "6127747", "6149738", "8625628", "10074877", "3676923", "3529834", "11591835", "10471426" ]

[ "Diazepam to improve acute stroke outcome: results of the early GABA-Ergic activation study in stroke trial. a randomized double-blind placebo-controlled trial.", "Prophylactic effect of neuroleptics in symptom-free schizophrenics.", "Ketazolam treatment for spasticity: double-blind study of a new drug.", "Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial.", "The efficacy and safety of clozapine versus chlorpromazine in geriatric schizophrenia.", "Treatment of spasticity with tizanidine in multiple sclerosis.", "A comparison of chlormethiazole and thioridazine in agitated confusional states of the elderly.", "The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T): final results.", "Remacemide hydrochloride: a double-blind, placebo-controlled, safety and tolerability study in patients with acute ischemic stroke." ]

[ "We tested whether diazepam, a GABA-ergic drug that also inhibits brain nitric monoxide formation, improves acute stroke prognosis.\n 880 patients, randomized within 12 h of acute stroke, received diazepam 10 mg or placebo by rectiole, as soon as possible, followed by 10-mg tablets twice daily for 3 days. Primary outcome was independence (Rankin score <3) at 3 months; secondary outcome was complete recovery (Barthel index >or=95 or Rankin score <or=1).\n Intention-to-treat analyses on all 849 patients with full follow-up (50.4% on diazepam): odds ratio (OR) 1.14, 95% CI 0.87-1.49 for primary endpoint, and an OR of 1.26 (0.90-1.76) for complete recovery, both favoring diazepam. Adjusted analyses for all stroke patients (843): OR 1.20 (0.87-1.65), and 1.25 (0.89-1.74), respectively, and for all infarct patients (748): OR 1.31 (0.93-1.85), and 1.46 (1.02-2.09; p=0.037), respectively. Analyses restricted to cardioembolic infarct patients (200) showed treatment benefit for the primary outcome: OR 2.26, 95% CI 1.07-4.76, p=0.032, and complete recovery: OR 2.65, 95% CI 1.06-6.59, p=0.037. About one third of ischemic stroke patients had 'any adverse event', without any difference between treatment groups. In 95 intracerebral hemorrhage patients, frequency of pneumonia and death were higher in the diazepam group than in the placebo group: 35 and 10%, 22 and 12%, respectively.\n Although point estimates favored diazepam treatment in various analyses, our data did not confirm our primary hypothesis. Diazepam treatment seems beneficial in cardioembolic infarct patients, is safe in acute ischemic stroke, but may better be avoided in intracerebral hemorrhage.\n Copyright (c) 2006 S. Karger AG, Basel.", "Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design. Patients were randomly assigned to the following drugs orally administered twice a day: placebo; diazepam 15 mg; imipramine 50 mg; chlorpromazine 75 mg; and haloperidol 3 mg. The number of days of remission for each patient was recorded. Since only two patients received all five drug treatments, the data were analyzed using the number of days allocated to the \"first assigned drugs\" only and the cross-over aspect of the experimental design was disregarded. All patients treated with either the placebo, diazepam or imipramine relapsed within a year. On the other hand, four patients treated with chlorpromazine, or with haloperidol, were in remission for more than 1 year. Fifty percent of the patients relapsed within 16 days with placebo; 88 days with diazepam; 30 days with imipramine; 165 days with chlorpromazine; and 74 days with haloperidol. Within a year, only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine. At the end of the 3-year trial, both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs. These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics.", "A minor tranquilizer, ketazolam, was tested in a double-blind, randomized, crossover study of 50 patients for its effects in neurologic spasticity. The drug was compared with diazepam (widely accepted as an effective antispasticity agent) and a placebo. The patients with spasticity were almost all cases of multiple sclerosis (24) or stroke (24). Thirty-nine patients completed the study. There was not statistically significant superiority of either diazepam or ketazolam, but both relieved symptoms significantly better than the placebo, as measured clinically and by electromyographic recording of deep tendon reflexes. Ketazolam is a relatively safe and clinically effective antispasticity agent (especially for patients with multiple sclerosis). The well-known \"big 3\"--dantrolene sodium, baclofen, and diazepam--produce large and small problems in many individual cases; hence, ketazolam now offers a safe and clinically useful alternative.", "To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay.\n A prospective, randomized, blinded, controlled clinical trial.\n A university hospital ICU.\n Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment.\n Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale).\n The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group.\n There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.", "There has been an absence of controlled studies focusing specifically on neuroleptic treatment in the elderly schizophrenic population. Therefore, we conducted a 12-week double-blind comparison study to assess the efficacy and tolerability of clozapine and chlorpromazine in a group of elderly inpatients with chronic schizophrenia.\n Forty-two elderly DSM-IV schizophrenic veterans were randomly assigned to clozapine or chlorpromazine and assessed for efficacy at baseline and at termination with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions scale (CGI). Side effects were also monitored. Medications were titrated, on the basis of clinical response and side effects, to a maximum dose of 300 mg/day of clozapine or 600 mg/day of chlorpromazine.\n The results suggest that both the chlorpromazine and clozapine groups improved their PANSS scores at termination compared with baseline, but the difference between the 2 groups was not statistically significant. The mean CGI scores reflecting severity of illness also demonstrated improvement in both groups over time. Both groups had similar incidences of side effects. One patient in each group had a life-threatening side effect. More patients taking clozapine had tachycardia and weight gain, while more chlorpromazine patients noted sedation.\n We concluded that both clozapine and chlorpromazine are effective treatments for psychosis and behavioral disturbances in geriatric schizophrenia. Both agents had similar incidences of side effects. With careful monitoring and titration of dosage, both clozapine and chlorpromazine were fairly well tolerated in this population.", "Spasticity is a frequent and often disabling symptom in MS patients. Current drugs used as antispastic agents include Dantrolene Sodium, Baclofen and Diazepam. Tizanidine (5-chloro-4-(2imidazolin-2 yl amino)-2,1,3-benzothialdiazole) is a new antispasticity agent that has purported central action. A double blind placebo controlled trial was performed to study the efficacy of this drug in MS patients. Sixty-six patients entered an eight week therapeutic trial and fifty-nine completed the trial. Patients were assessed at 0, 2, 3 and 8 weeks of therapy for clinical effects. Electrophysiologic tests were performed at 0 and 8 weeks. A statistically significant benefit was noted in spastic muscle groups in the legs with concomitant significant reduction in hyperactive stretch reflexes and ankle clonus. Side effects most frequently cited included dry mouth and drowsiness. Two patients developed elevated liver function test that decreased with cessation of therapy. Other clinical details, side effects and electrophysiologic data will be presented. Tizanidine appears to reduce clinical spasticity and hyperreflexia in MS patients although no change in functional status was detected. Tizanidine may well serve as an alternate antispastic agent, alone or in combination with other agents.", "Chlormethiazole and thioridazine were found to be equally effective in the management of the agitational component of agitated confusional states in the elderly. Confusion and nocturnal awakening were found to be controlled more effectively with chlormethiazole than with thioridazine. Chlormethiazole treatment also resulted in significant reductions in physical disability as assessed by the Clifton Behaviour Rating Scale. A greater incidence of adverse effects was associated with thioridazine treatment.", "To assess the safety of tissue-type plasminogen activator (t-PA) plus clomethiazole in patients with acute ischemic stroke and determine the feasibility of combination stroke therapy.\n Clomethiazole is a neuroprotectant that appeared to improve outcome in patients with clinical deficits of a major stroke (total anterior circulation syndrome [TACS]) in a previous study, the Clomethiazole Acute Stroke Study (CLASS). Combining a neuroprotectant such as clomethiazole with thrombolysis may augment the beneficial effects of the two agents. CLASS-t-PA (CLASS-T) was a pilot study to explore the safety of the combination and the feasibility of performing combination treatment in the setting of acute ischemic stroke.\n In a randomized, double-blind design (stratified for age, severity at admission, and time since onset of stroke), all patients received 0.9 mg/kg t-PA beginning within 3 hours of stroke onset and then either 68 mg/kg clomethiazole (n = 97) IV over 24 hours or placebo (n = 93) beginning within 12 hours of stroke onset. Patients were followed for 90 days. The main measures of safety were mortality and serious adverse events, and the main measure of functional outcome was the Barthel Index.\n The number of serious adverse event reports was 47 in the clomethiazole group and 48 in the placebo group. Death during the 90 days after treatment occurred in 15 clomethiazole and nine placebo patients (p = 0.26). Sedation was reported as an adverse event during therapy in 42% of clomethiazole patients vs 13% of placebo patients. The proportion of patients with TACS was 53% in the clomethiazole group and 41% in the placebo group. In the TACS subgroup, 52.9% of the clomethiazole patients scored a Barthel Index greater than 60 vs 44.7% of placebo patients (odds ratio 1.39; 95% CI 0.60 to 3.23).\n In this pilot study, there were no safety concerns related to the combination of t-PA and clomethiazole. The combination paradigm proved feasible, although many patients received clomethiazole several hours after thrombolysis; future studies must require prompt administration of the neuroprotectant either before or during administration of the thrombolytic. Patients with major strokes (TACS) may have the potential to benefit from the combination of t-PA and clomethiazole.", "Remacemide hydrochloride and its principal active desglycinyl metabolite are low-affinity noncompetitive N-methyl-D-aspartate (NMDA)-receptor channel blockers. Remacemide hydrochloride has demonstrated neuroprotection in animal models of hypoxia and ischemic stroke. This study assessed the safety, tolerability, and pharmacokinetics of ascending doses of remacemide hydrochloride in patients with recent onset (within 12 hours) ischemic stroke.\n This was a placebo-controlled, dose escalating, parallel group study. Groups of 8 patients (6 active, 2 placebo) were planned to receive twice-daily treatment, with l00 mg, 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg remacemide hydrochloride given as 2 intravenous infusions followed by 6 days' oral treatment. Patients who were unable to swallow discontinued study medication but continued to be monitored for safety; these patients were replaced. A CT or MRI scan was performed within 48 hours of admission to establish the cause of focal neurological deficit. Patients with ischemic stroke continued in the study. Patients with other causes of focal neurological deficit were withdrawn and replaced. Because the frequency of dysphagia after stroke in the first dose group (100 mg BID) was higher than had been anticipated, the protocol was amended so that subsequent dose groups received 6 intravenous infusions (2 doses per day for 3 days). Neurological and functional outcome data were collected, but the study was not powered to demonstrate drug efficacy. Patient safety was assessed by clinical observation, laboratory tests, and ECGs, while tolerability was assessed by recording adverse events. Blood sampling was included to determine plasma concentrations of remacemide and the desglycinyl metabolite at fixed points during the dosing period.\n The most common adverse events considered by the investigator to be possibly treatment related were related to the central nervous system (CNS), and these events appeared to increase with dose. Four patients were withdrawn from the study because of CNS-related events: 1 in the placebo group, 1 in the 500 mg BID group, and 2 in the 600 mg BID group. Infusion site reactions and gastrointestinal upset were also reported and considered to be treatment related. One patient in the placebo group and 4 patients in the 600 mg BID dose group experienced vomiting, whereas this event was not reported by patients in the other dose groups.\n On the evidence of this study, the maximum well-tolerated dose for remacemide hydrochloride in acute stroke is 400 mg BID. Doses of 200 mg BID or higher attained the putative neuroprotective plasma concentrations of remacemide predicted from animal models (250 to 600 ng/mL). The expected gradual accumulation of active metabolite might suggest that optimal neuroprotective concentrations are unlikely to be achieved within the early hours of treatment at this dose. However, plasma concentrations do not directly reflect brain concentrations, because studies in rats show that remacemide and the desglycinyl metabolite rapidly reach comparable brain concentrations within 1 hour, despite a lower plasma concentration of the metabolite." ]

[ "10983198", "12197996", "12600852", "15531671", "11976158", "17100860", "20851308", "14633807", "20087379" ]

[ "A prospective study of whole-grain intake and risk of type 2 diabetes mellitus in US women.", "Whole-grain intake and the risk of type 2 diabetes: a prospective study in men.", "Whole-grain and fiber intake and the incidence of type 2 diabetes.", "Changes in whole-grain, bran, and cereal fiber consumption in relation to 8-y weight gain among men.", "Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults.", "An educational programme for peer review groups to improve treatment of chronic heart failure and diabetes mellitus type 2 in general practice.", "Randomized, controlled trial promotes physical activity and reduces consumption of sweets and sodium among overweight and obese adults.", "The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year results on diet and physical activity.", "Effects of controlled school-based multi-component model of nutrition and lifestyle interventions on behavior modification, anthropometry and metabolic risk profile of urban Asian Indian adolescents in North India." ]

[ "This study examined the association between intake of whole vs refined grain and the risk of type 2 diabetes mellitus.\n We used a food frequency questionnaire for repeated dietary assessments to prospectively evaluate the relation between whole-grain intake and the risk of diabetes mellitus in a cohort of 75,521 women aged 38 to 63 years without a previous diagnosis of diabetes or cardiovascular disease in 1984.\n During the 10-year follow-up, we confirmed 1879 incident cases of diabetes mellitus. When the highest and the lowest quintiles of intake were compared, the age and energy-adjusted relative risks were 0.62 (95% confidence interval [CI] = 0.53, 0.71, P trend < .0001) for whole grain, 1.31 (95% CI = 1.12, 1.53, P trend = .0003) for refined grain, and 1.57 (95% CI = 1.36, 1.82, P trend < .0001) for the ratio of refined- to whole-grain intake. These findings remained significant in multivariate analyses. The findings were most evident for women with a body mass index greater than 25 and were not entirely explained by dietary fiber, magnesium, and vitamin E.\n These findings suggest that substituting whole- for refined-grain products may decrease the risk of diabetes mellitus.", "Certain dietary components may play a role in the prevention of type 2 diabetes.\n We examined prospectively the associations between whole- and refined-grain intake and the risk of type 2 diabetes in a large cohort of men.\n Men from the Health Professionals Follow-up Study without a history of diabetes or cardiovascular disease in 1986 (n = 42898) were followed for </=12 y. Intakes of whole and refined grains, measured every 4 y by use of food-frequency questionnaires, were used to predict subsequent type 2 diabetes risk through multivariate analysis.\n We ascertained 1197 cases of incident type 2 diabetes. After adjustment for age; physical activity; cigarette smoking; alcohol consumption; family history of diabetes; and fruit, vegetable, and energy intakes, the relative risk of type 2 diabetes was 0.58 (95% CI: 0.47, 0.70; P for trend < 0.0001) comparing the highest with the lowest quintile of whole-grain intake. The association was moderately attenuated when additionally adjusted for body mass index (relative risk: 0.70; 95% CI: 0.57, 0.85; P for trend = 0.0006). Intake of refined grains was not significantly associated with risk of type 2 diabetes. After further adjustment for magnesium intake, cereal fiber intake, and glycemic load, the association between whole grains and type 2 diabetes was attenuated and the trend no longer significant.\n In men, a diet high in whole grains is associated with a reduced risk of type 2 diabetes in men that may be mediated by cereal fiber. Efforts should be made to replace refined-grain with whole-grain foods.", "Epidemiologic evidence of a preventive effect of whole grain against type 2 diabetes is mainly based on data from women. Information specific to men and women is needed.\n The objective was to study the relation between the intake of whole grain and fiber and the subsequent incidence of type 2 diabetes.\n The design was a cohort study of 2286 men and 2030 women aged 40-69 y and initially free of diabetes. Food consumption data were collected from 1966 through 1972 with the use of a dietary history interview covering the habitual diet during the previous year. During a 10-y follow-up, incident type 2 diabetes cases were identified in 54 men and 102 women from a nationwide register.\n Whole-grain consumption was associated with a reduced risk of type 2 diabetes. The relative risk (adjusted for age, sex, geographic area, smoking status, body mass index, energy intake, and intakes of vegetables, fruit, and berries) between the highest and lowest quartiles of whole-grain consumption was 0.65 (95% CI: 0.36, 1.18; P for trend = 0.02). Cereal fiber intake was also associated with a reduced risk of type 2 diabetes. The relative risk between the extreme quartiles of cereal fiber intake was 0.39 (95% CI: 0.20, 0.77; P = 0.01).\n An inverse association between whole-grain intake and the risk of type 2 diabetes was found. The similar result for cereal fiber intake suggests that the whole-grain association is due to cereal fiber or another factor related to cereal fiber intake.", "Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse, and characterization of this association has been obscured by methodologic inconsistencies in the assessment of whole grains.\n We aimed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men.\n The study was conducted in a prospective cohort of 27 082 men aged 40-75 y at baseline in 1986. Data on lifestyle factors were obtained periodically by using self-reported questionnaires, and participants measured and reported their body weight in 1986 and 1994.\n In multivariate analyses, an increase in whole-grain intake was inversely associated with long-term weight gain (P for trend < 0.0001). A dose-response relation was observed, and for every 40-g/d increment in whole-grain intake from all foods, weight gain was reduced by 0.49 kg. Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain (P for trend = 0.01), and, for every 20 g/d increase in intake, weight gain was reduced by 0.36 kg. Changes in cereal and fruit fiber were inversely related to weight gain. No associations were observed between changes in refined-grain or added germ consumption and body weight.\n The increased consumption of whole grains was inversely related to weight gain, and the associations persisted after changes in added bran or fiber intakes were accounted for. This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain.", "Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of type 2 diabetes and heart disease.\n We tested the hypothesis that whole-grain consumption improves insulin sensitivity in overweight and obese adults.\n This controlled experiment compared insulin sensitivity between diets (55% carbohydrate, 30% fat) including 6-10 servings/d of breakfast cereal, bread, rice, pasta, muffins, cookies, and snacks of either whole or refined grains. Total energy needs were estimated to maintain body weight. Eleven overweight or obese [body mass index (in kg/m(2)): 27-36] hyperinsulinemic adults aged 25-56 y participated in a randomized crossover design. At the end of each 6-wk diet period, the subjects consumed 355 mL (12 oz) of a liquid mixed meal, and blood samples were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered.\n Fasting insulin was 10% lower during consumption of the whole-grain than during consumption of the refined-grain diet (mean difference: -15 +/- 5.5 pmol/L; P = 0.03). After the whole-grain diet, the area under the 2-h insulin curve tended to be lower (-8832 pmol.min/L; 95% CI: -18720, 1062) than after the refined-grain diet. The rate of glucose infusion during the final 30 min of the clamp test was higher after the whole-grain diet (0.07 x 10(-4) mmol.kg(-1).min(-1) per pmol/L; 95% CI: 0.003 x 10(-4), 0.144 x 10(-4)).\n Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease.", "Peer review groups are considered helpful for quality improvement in primary care. An interactive educational programme for small peer groups was developed, focusing on the implementation of newly developed treatment guidelines. The aim is to evaluate the effect of the programme on adherence to treatment guidelines in general practice.\n A cluster randomized trial using a balanced incomplete block design was used; one arm received a programme on treatment of chronic heart failure (CHF), the other on hypertension treatment in diabetes mellitus type 2 (T2DM). A random sample of 10 CHF and 10 T2DM patients per GP was drawn, for whom data were extracted from electronic patient records 1 years before and 6 months after the intervention. The outcomes were prescribing of ACE inhibitors, and antihypertensive treatment in T2DM. The effect was analysed separately for both programmes using multilevel regression models.\n All 27 peer review groups in one region in the Netherlands were randomized, of which 16 participated. No significant effects were observed in the CHF group or in the T2DM group. The opportunity for change was limited, as only 53% of the CHF patients and 60% of the T2DM patients had a contact with their GP between the intervention and follow-up measurement.\n The peer review programme was not successful for changing the treatment of chronic patients, although the programme focused on dealing with barriers perceived by the participants. Not all problems perceived can be solved in a peer group discussion.", "The present study sought to assess the impact of an intervention to reduce weight and control risk factors of noncommunicable chronic diseases in overweight or obese adults who are users of primary and secondary healthcare units of the public health system of Pelotas, Brazil. We hypothesized that individuals who received an educational intervention regarding how to lose weight and prevent other noncommunicable chronic disease risk factors through nutrition would lose weight and acquire active habits during leisure time more frequently than individuals under regular care. Two hundred forty-one participants from the Nutrition Outpatient Clinic of the Medical Teaching Hospital of the Federal University of Pelotas, Brazil, aged 20 years or older and classified as overweight or obese were randomly allocated to either the intervention group (IG; n = 120) or control group (CG; n = 121). The IG received individualized nutritional care for 6 months, and the CG received individualized usual care of the health services. Intention-to-treat analyses showed that at 6 months, mean fasting glycemia and daily consumption of sweet foods and sodium were reduced, and the time spent on physical leisure activity was increased in IG. Analysis of adherence to the protocol of the study revealed that individuals from IG had lost more in body weight, waist circumference, and fasting glucose compared to the CG. Leisure time physical activity increased in IG. Individuals adhered equally to the dietetic recommendations, irrespective of the nutrition approach that was used.\n Copyright © 2010 Elsevier Inc. All rights reserved.", "To describe the 1) lifestyle intervention used in the Finnish Diabetes Prevention Study, 2) short- and long-term changes in diet and exercise behavior, and 3) effect of the intervention on glucose and lipid metabolism.\n There were 522 middle-aged, overweight subjects with impaired glucose tolerance who were randomized to either a usual care control group or an intensive lifestyle intervention group. The control group received general dietary and exercise advice at baseline and had an annual physician's examination. The subjects in the intervention group received additional individualized dietary counseling from a nutritionist. They were also offered circuit-type resistance training sessions and advised to increase overall physical activity. The intervention was the most intensive during the first year, followed by a maintenance period. The intervention goals were to reduce body weight, reduce dietary and saturated fat, and increase physical activity and dietary fiber.\n The intervention group showed significantly greater improvement in each intervention goal. After 1 and 3 years, weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group, respectively. Measures of glycemia and lipemia improved more in the intervention group.\n The intensive lifestyle intervention produced long-term beneficial changes in diet, physical activity, and clinical and biochemical parameters and reduced diabetes risk. This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system.", "To study the effectiveness of a multi-component intervention model of nutrition and lifestyle education on behavior modification, anthropometry and metabolic risk profile of urban Asian-Indian adolescents in North India.\n Two schools matched for student strength and middle socioeconomic strata were randomly allocated to intervention and control group. Changes in nutrition-related knowledge, attitude, lifestyle practices, food frequency and body image of eleventh-grade students (15-17 years) in both schools were tested using a validated questionnaire. Anthropometric and biochemical measurements were made using standard methods. Segmental body composition analysis was carried out using an 8-electrode multifrequency bioelectrical impedance method of body fat estimation.\n At 6 months follow-up, significant improvement in several domains of knowledge was observed in intervention children (n=99; males=60; females=39) as compared with control school children (n=102; males=61; females=41). In the intervention group, significantly lower proportion of children consumed aerated drinks (15.1%; P<0.001) and energy-dense unhealthy foods (8.9%; P=0.03), whereas significantly higher proportion brought tiffin (packed lunch) to school (14.9%; P=0.004) and brought a fruit in their tiffin (30.7%; P<0.001) as compared with the control group. Significant decrease in mean waist circumference (P=0.02, 95% confidence interval (CI)=-2.43,-0.17), sagittal abdominal diameter (P<0.001, 95% CI=-0.82,-0.09), waist-to-hip ratio (P=0.02, 95% CI=-0.03,-0.004) and fasting blood glucose (P=0.05, 95% CI=-0.09, 5.00) was seen in intervention as compared with control school children.\n Multi-component model of nutrition and lifestyle education was successful in improving the nutrition-related knowledge, eating habits and lifestyle practices, and resulted in beneficial changes in anthropometric and biochemical profiles of the Asian Indian adolescents. This model should be applied on countrywide basis to prevent obesity and diabetes." ]

[ "9754744", "12426500", "15910477", "10080304", "3479490", "10570589", "11725662", "1803333", "15101598" ]

[ "Survival of three types of veneer restorations in a clinical trial: a 2.5-year interim evaluation.", "Three-year clinical comparison of survival of endodontically treated teeth restored with either full cast coverage or with direct composite restoration.", "Endodontic complications after plastic restorations in general practice.", "Six-year follow-up of titanium and high-gold porcelain-fused-to-metal fixed partial dentures.", "Clinical performance of sealed composite restorations placed over caries compared with sealed and unsealed amalgam restorations.", "Clinical performance and caries inhibition of resin-modified glass ionomer cement and amalgam restorations.", "A two-year randomized, controlled clinical evaluation of bonded amalgam restorations.", "A clinical and histological evaluation of conservative pulpal therapy in human teeth.", "Cemented versus screw-retained implant-supported single-tooth crowns: a 4-year prospective clinical study." ]

[ "In this clinical trial, 180 veneer restorations (VRs) were evaluated. The purpose of the study was to collect survival data and to find possible relations between survival and (1) 'type of VR', (2) 'preparation design', (3) 'operator' and (4) the patient-related variables 'tooth-type' and 'vitality of the tooth'.\n The restorations were provided by seven dentists in 1 12 patients on central and lateral maxillary incisors. Experimental variables were: 'type of VR' (either direct resin composite (DC), indirect resin composite (IC) or porcelain (P)), 'preparation design' (with and without incisal overlap) and 'operator'. Failures were recorded at two levels: absolute failure (need for new restoration) and relative failure (need for repair). Survival was defined at three levels: (1) survival of original restoration (Sr, endpoints: 'absolute' failures), (2) functional survival (Sf, endpoints: 'relative' failures) and (3) overall survival (SO, endpoints: both 'absolute-' and 'relative failures').\n The variable 'type of VR' showed significant influence on Sf and So but not on Sr. Sf and So rates of P, IC and DC were, respectively: Sf-P, 94%; So-P, 94%; Sf-IC, 94%; So-IC, 90%; Sf-DC, 80%; So-DC, 74%. VRs on vital teeth showed a significantly better survival than VRs on non-vital teeth at all survival levels.\n Preparation of the incisal edge for incisal coverage is considered to be unnecessary to assure or improve the strength of VRs. Veneers on non-vital teeth showed higher risk to fail than veneers placed on vital teeth. Porcelain veneers showed the best overall survival.", "Little information exists regarding the outcome of crown build-ups on endodontically treated teeth restored with metal-ceramic crowns or with only a direct-placed composite.\n The aim of this study was to evaluate the clinical success rate of endodontically treated premolars restored with fiber posts and direct composite restorations and compare that treatment with a similar treatment of full-coverage with metal-ceramic crowns.\n Subjects included in this study had one maxillary or mandibular premolar for which endodontic treatment and crown build up was indicated and met specific inclusion/exclusion criteria. Only premolars with Class II carious lesions and preserved cusp structure were included. Subjects were randomly assigned to 1 of the following 2 experimental groups: (1) teeth endodontically treated and restored with adhesive techniques and composite or (2) teeth endodontically treated, restored with adhesive techniques and composite, and then restored with full-coverage metal-ceramic crowns. Sixty teeth were included in the first group and 57 in the second. All restorations were performed by one operator. Causes of failure were categorized as root fracture, post fracture, post decementation, clinical and/or radiographic evidence of marginal gap between tooth and restoration, and clinical and/or radiographic evidence of secondary caries contiguous with restoration margins. Subjects were examined for the listed clinical and radiographic causes of failure by 2 calibrated examiners at intervals of 1, 2, and 3 years. Exact 95% confidence intervals for the difference between the 2 experimental groups were calculated.\n At the 1-year recall, no failures were reported. The only failure modes observed at 2 and 3 years were decementations of posts and clinical and/or radiographic evidence of marginal gap between tooth and restoration. There was no difference in the failure frequencies of the 2 groups (95% confidence interval, -17.5 to 12.6). There was no difference between the number of failures caused by post decementations and the presence of marginal gaps observed in the 2 groups (95% confidence intervals, -9.7 to 16.2 and -17.8 to 9.27).\n Within the limitations of this study, the results upheld the research hypothesis that the clinical success rates of endodontically treated premolars restored with fiber posts and direct composite restorations after 3 years of service were equivalent to a similar treatment of full coverage with metal-ceramic crowns.", "To test the hypothesis that dentine and pulp protection by conditioning-and-sealing is no less effective than using a conventional calcium hydroxide lining.\n A cohort of healthy adults requiring a new or replacement restoration in a posterior tooth was recruited in six general practices. All procedures received local Ethics Committee approval. Exclusion criteria included signs and symptoms of pulp necrosis or inflammation, and patients unable to commit to a long-term trial. Cavity preparations were randomized to receive a calcium hydroxide lining or conditioning-and-sealing with a smear-removing bonding system. Choice of bulk restorative material (composite resin or amalgam) was at the discretion of the dentist. The key outcome measure was evidence of pulpal breakdown identified at unscheduled (emergency) or scheduled recall examinations. Postoperative sensitivity was recorded on 100 mm VAS at 24 h, 4 days and 7 days. Pulp status was assessed at 6, 12, 24 and 36 month recall, and at any emergency recall appointment. The relationship between pre-treatment and treatment variables and pulp breakdown was assessed by logistic regression (P = 0.05).\n A total of 602 teeth were recruited, with comparable numbers of cavities lined (288, 47.8%) or conditioned and sealed (314, 52.2%). The majority (492, 81.7%) were replacement restorations, and amalgam was the most common bulk restorative material (377, 62.6%). A total of 390 (64.8%) restored teeth were reviewed at 6 months, 307 (51%) at 12 months, 363 (60.3%) at 24 months, and 279 (46.3%) at 36 months post-restoration. Sixteen cases of pulp breakdown were identified within 36 months of restoration placement, 11 presenting as emergencies and five detected at routine recall examination. Logistic regression showed that preoperative pain, cavity treatment by lining or conditioning-and-sealing and the use of rubber dam isolation had no association with pulp breakdown. Pulp breakdown was associated with deep or pulpally exposed cavities (P < 0.001, odds ratio 7.8) and with composite rather than amalgam restorations (P = 0.001, odds ratio 2.13). Re-coding to identify teeth with pulp exposures revealed that pulpal exposure was the key determinant of adverse pulp outcomes (P < 0.0001, odds ratio 28.4) and that composite resin restorations were again more likely to be associated with pulp breakdown than amalgam (P = 0.017, odds ratio 3.92).\n Considered within the context of routine primary dental care: Dentists can be confident that pulps will be equally well protected from post-restorative breakdown up to 36 months by calcium hydroxide lining and conditioning-and-sealing with adhesive resins. Residual dentine thickness appears to be a key determinant of pulp responses after restorative dental treatment. In deep and pulpally exposed cavities in posterior teeth, composites were associated with more pulpal breakdown than amalgams.", "In a randomized clinical study 47 titanium and gold-alloy fixed partial dentures (FPDs) were placed during a 1-year period. In the titanium group (n = 22) all metal substructures were made of unalloyed titanium. The titanium substructures were fabricated by copy milling, spark erosion and laser welding (Procera, Nobelpharma). Ceramic veneering was carried out with Duceratin titanium ceramics (Ducera, Germany). In the control group (n = 25) the high-gold alloy Degudent U (Degussa, Germany) and Vita VMK 68 ceramics (Vita, Germany) were used. The longest observation time was 6 years. Only one FPD had to be removed due to metal-ceramic failure (titanium group). The clinical performance of all 125 porcelain-fused-to-metal (PFM) veneers with respect to the longevity of the metal-ceramic compound was described by Kaplan-Meyer survivor analyses. Relating survival to a completely intact ceramic veneer, the 5-year survivor rate was 84% for titanium and 98% for the high-gold alloy. PFM titanium restorations exhibited a significantly increased risk of metal-ceramic failure. However, concerning defects requiring removal, no significant differences in titanium versus high-gold alloy occurred. There were no significant differences in the survival distributions between crowns and pontics within the two groups.", "The 2-year clinical evaluations of paired occlusal restorations are presented. Each study participant received a sealed composite restoration placed over a carious lesion and either a traditional outline-form (unsealed) amalgam or an ultraconservative sealed amalgam restoration. Caries was removed before placement of both types of amalgam restorations. No important clinical differences developed among the three groups of restorations.", "The authors clinically examined two restorative materials to evaluate their effectiveness in Class II restorations in primary molars and their ability to inhibit recurrent caries.\n Forty subjects, each in need of two Class II restorations in primary molars, took part in this study. Each patient received one Class II restoration of resin-modified glass ionomer cement and one of amalgam. The authors evaluated the restorations at six-month, one-year, two-year and three-year recall appointments. On exfoliation, teeth with experimental restorations were retrieved and microscopically examined for inhibition of demineralization at restoration margins.\n The results of the clinical evaluation demonstrated no significant differences between the resin-modified glass ionomer cement restorations and the amalgam restorations (P < .05). Polarized light microscopic examination of the returned teeth that were restored as a part of this study indicated that the resin-modified glass ionomer cement had significantly less enamel demineralization at restoration margins than did amalgam (P < .0001).\n The resin-modified glass ionomer cement functioned clinically as well as amalgam for Class II restorations in primary molars. However, the resin-modified glass ionomer exhibited significantly less enamel demineralization at restoration margins than did amalgam.\n Resin-modified glass ionomer cement restorative material functions well for Class II restorations in primary molars and exhibits less recurrent caries at restoration margins than does amalgam.", "The clinical performance of adhesively bonded dental amalgam restorations was compared with that of traditionally placed non-bonded control amalgams in a randomized prospective study.\n One-hundred thirteen Class II Dispersalloy amalgams were placed in permanent molars and premolars of 31 (21 males, 10 females) human subjects with their informed consent. By random assignment, 60 amalgam restorations were adhesively bonded using ED Primer and Panavia 21 TC (both Kuraray Co, Japan), and 53 traditional non-bonded restorations were placed. Most preparations involved replacement of defective amalgam restorations. Clinical recalls were conducted by experienced evaluators using modified USPHS criteria for occlusal and proximal anatomic form, occlusal and proximal marginal adaptation, and occlusal and proximal surface roughness.\n For the categories of anatomic form, marginal adaptation, surface quality, and temperature sensitivity, there were no significant differences between bonded and non-bonded amalgam restorations (chi-square analysis, p > 0.05). Three non-bonded restorations were lost at 4, 7, and 24 months from preparations with no deliberate retention.\n After two years' clinical service, there were no failures among the amalgam restorations adhesively bonded using ED Primer and Panavia 21 TC, but three non-bonded restorations failed due to lack of retention. For traditional preparations, adhesively bonded amalgams of the type investigated perform as well as non-bonded amalgams over two years' clinical service.", "Three intermediary base materials, a zinc oxide-eugenol (Cavitec) and two calcium hydroxide liners (Life and Dycal), were selected at random for use as a base beneath amalgam or composite restorations on humans following complete caries removal. Life and Dycal, selected at random, were also used as direct and indirect pulp capping agents as clinically indicated. Clinical evaluations of signs and symptoms were made before treatment and at one-week, six-month, and one-year intervals following treatment. Histological evaluations were performed on three complete caries removal teeth and 18 direct pulp capping teeth six months following treatment. No significant differences in clinical symptomatology resulted between the materials in the complete caries removal group or the indirect and direct pulp capping groups.", "The purpose of this controlled prospective clinical study was to compare cemented and screw-retained implant-supported single-tooth crowns followed for 4 years following prosthetic rehabilitation with respect to peri-implant marginal bone levels, peri-implant soft tissue parameters, and prosthetic complications.\n Twelve consecutive patients were selected from a patient population attending the Implantology Department at the University of Padova. They all presented with single-tooth bilateral edentulous sites in the canine/premolar/molar region with adequate bone width, similar bone height at the implant sites, and an occlusal scheme that allowed for the establishment of identical occlusal cusp/fossa contacts. Each patient received 2 identical implants (1 in each edentulous site). One was randomly selected to be restored with a cemented implant-supported single-tooth crown, and the other was restored with a screw-retained implant-supported single-tooth crown. Data on peri-implant marginal bone levels and on soft tissue parameters were collected 4 years after implant placement and analyzed to determine whether there was a significant difference with respect to the method of retention (cemented versus screw-retained).\n All patients completed the study. All 24 implants survived, resulting in a cumulative implant success rate of 100%. Statistical analysis revealed no significant differences between the 2 groups with respect to peri-implant marginal bone levels and soft tissue parameters.\n The data obtained with this study suggested that the choice of cementation versus screw retention for single-tooth implant restorations is likely not based on clinical results but seems to be based primarily on the clinician's preference.\n Within the limitations of this study, the results indicate that there was no evidence of different behavior of the peri-implant marginal bone and of the peri-implant soft tissue when cemented or screw-retained single-tooth implant restorations were provided for this patient population." ]

[ "11149033", "9972405", "11913801", "12607659", "2571469", "9489309", "11132739", "11803323", "17130328" ]

[ "Perioperative renal protection in patients with obstructive jaundice using drug combinations.", "Tenoxicam does not alter renal function during anaesthesia in normal individuals.", "The effects of fenoldopam on renal function in patients undergoing elective aortic surgery.", "Pain treatment with a COX-2 inhibitor after coronary artery bypass operation: a randomized trial.", "The use of anxiolytic and parasympathomimetic agents in the treatment of postoperative urinary retention following anorectal surgery. A prospective, randomized, double-blind study.", "[Does the preoperative administration of ketorolac improve postoperative analgesia].", "Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery.", "Renal dose dopamine in open heart surgery. Does it protect renal tubular function?", "Minor infection encouraged by steroid administration during cardiac surgery." ]

[ "The effectiveness of dopamine alone or in combination with mannitol or furosemide in preventing postoperative renal dysfunction in patients with obstructive jaundice was assessed in this study.\n Forty patients having obstructive jaundice were randomly allocated into 4 equal groups. Preoperative hydration was performed by infusing all patients 1L of 5% dextrose the night before surgery and another 1L in the morning before surgery. Intra- and postoperative maintenance of adequate intravascular volume was assured by fluid and blood replacement guided by the monitoring of central venous pressure urine output and blood pressure. The 1st group was kept as a control. The other 3 groups received dopamine 2.5 micrograms/kg/min for 2 postoperative days starting before surgery. The 2nd group was maintained on dopamine alone, while mannitol (0.25 g/kg), every 12 hours for 2 postoperative days, was added to the 3rd group. Similarly furosemide (1 mg/kg) every 12 hours for 2 postoperative days, was infused to the patients of the 4th group. Postoperative renal functions were assessed by 24-hour urine output, serum creatinine, creatinine clearance and urine to plasma osmolality ratio.\n All these tests did not show significant changes in the 1st, 2nd and 7th postoperative days. Only transient decreased creatinine clearance and elevated serum creatinine were observed in the patients of the 4th group in the 1st and 2nd postoperative days. This may be attributed to fluid imbalance induced by furosemide in these patients who were older than the other groups.\n The study showed that careful attention to perioperative hydration is the cornerstone in preserving adequate renal function following surgery in patients with obstructive jaundice. Administration of dopamine alone or in combination with mannitol or furosemide did not confer more renal protection.", "Anaesthesia and surgery alter renal function. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs (NSAIDs) administered with anaesthesia may further compromise renal function.\n To study the effects of tenoxicam (NSAID) administered immediately prior to anaesthesia on renal function in normal individuals undergoing routine surgery.\n A randomised single blind placebo controlled study comparing tenoxicam (40 mg intravenously) with placebo was carried out in 20 healthy (ASA I) patients undergoing lower spinal surgery. Glomerular filtration rate (GFR) was determined by creatinine clearance and renal tubular function measured as osmolar and free water clearance.\n GFR fell by 60% at the end of surgery but returned to pre-operative values by six hours post-operatively. There was no difference between placebo or tenoxicam with regard to changes in GFR. Tubular function was not altered by tenoxicam.\n Current clinical practice of using NSAIDs for post-operative analgesia in low risk individuals appears to have no adverse effects on renal function.", "Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Our hypothesis was that the renal vasodilating and natriuretic effects of fenoldopam mesylate, a selective dopamine (DA1) agonist, would preserve renal function in patients undergoing elective infrarenal aortic cross-clamping.\n A prospective, randomized, double blind controlled clinical trial was performed. Twenty-eight ASA II-III patients undergoing elective aortic surgery requiring infrarenal aortic cross-clamping were studied. According to random allocation, patients received either fenoldopam (0.1 microg kg(-1) min(-1)) or placebo intravenously prior to surgical skin incision until release of the aortic clamp. Plasma creatinine, creatinine clearance, urinary output, fractional excretion of sodium, and free water clearance were measured: (a) prior to admission to hospital; (b) during the period from insertion of the urinary catheter until application of the aortic cross-clamp; (c) during the period of aortic cross-clamping; (d) 0-4 h, and (e) 4-8 h after release of the clamp and on days 1, 2, 3, and 5 postoperatively.\n Fenoldopam (0.1 microg kg(-1)min(-1)) administration was not associated with haemodynamic instability. On application of the aortic cross-clamp creatinine clearance decreased significantly in the placebo (83 +/- 20 to 42 +/- 29 mL min(-1) (mean +/- SD)) (P < 0.01) but not in the fenoldopam group, and this decrease persisted for at least 8 h after release of the cross-clamp (83 +/- 20 to 54 +/- 33 mL min(-1) (mean +/- SD)) (P < 0.05). Plasma creatinine concentration increased significantly from baseline on the first postoperative day in the placebo group (87 +/- 12 to 103 +/- 28 micromolL(-1) (mean +/- SD)) (P < 0.01) but not in the fenoldopam group.\n These findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect during and after infrarenal aortic cross-clamping.", "Adequate analgesic medication is mandatory after cardiac operations. Cyclooxygenase-2 inhibitors represent a new therapeutic option, acting primarily on the response to inflammation.\n We compared a cyclooxygenase-2 inhibitor (etodolac) with two traditional drugs: a nonselective cyclooxygenase inhibitor (diclofenac) and a weak opioid (tramadol) on postoperative pain and renal function in patients undergoing coronary artery bypass operations. Sixty consecutive patients were randomized into three groups: (1) group A patients who received tramadol; (2) group B patients who received diclofenac; and (3) group C patients who received etodolac. For measurement of analgesic effect, the visual analogue scale was assessed up to postoperative day 4. Creatinine-clearance was determined before and at the end of study medication, and serum creatinine and urea were monitored daily for renal effects. Study medication was given on postoperative days 2 and 3. Side effects and additional pain medication were recorded.\n The visual analogue scale was lower in group C (p < 0.05) from postoperative days 2 to 4 and in group B (p < 0.05) from postoperative days 3 to 4 compared with group A. Amount of additional pain medication and incidence of side effects were significantly less in group C compared with group A. We observed a short-lasting elevation of serum creatinine and urea in groups B and C compared with group A (p < 0.05).\n At the doses analyzed, etodolac and diclofenac produced better postoperative pain relief with less side-effects than tramadol. A short-lasting impairment of renal function was found in patients treated with etodolac and diclofenac.", "Approximately 30 percent of patients undergoing anorectal surgery will develop acute urinary retention. The cause of this complication is poorly understood. Anxiety, anal distention, bladder distention as a result of vigorous hydration during surgery, and reflex inhibition of the urinary bladder detrusor muscle secondary to pain have been postulated as contributing factors. A four-armed prospective, double-blind, randomized trial was carried out to determine whether an anxiolytic agent (midazolam, 5 mg intramuscularly) and/or a parasympathomimetic agent (bethanechol, 10 mg subcutaneously) reduce the incidence of postoperative urinary retention following anorectal surgery. One hundred thirty-two patients (ages, 18 to 50 years), in acute urinary retention 6 to 12 hours following anorectal surgery, were enrolled. Sixty-nine percent of patients responded to bethanechol. Side effects were minimal. Midazolam alone had no effect on retention. Bethanechol and midazolam in combination resulted in less retention than midazolam and a placebo (P less than 0.05). Bethanechol alone was better than a placebo (P less than 0.002). Mean intraoperative intravenous fluid volume for the entire study group was 900 cc. Initial postoperative urinary volumes of patients who failed the treatment protocol were significantly higher than in those responding to bethanechol (mean of 527 cc vs. 241 cc, P less than 0.001). The use of an anxiolytic agent was not effective in the treatment of postoperative urinary retention. Bladder distention may increase the incidence of urinary retention. Bethanechol, in a dose of 10 mg subcutaneously, significantly lowered the incidence of postoperative urinary catheterization and should be considered as initial treatment of postoperative urinary retention following anorectal surgery.", "1) To verify the usefulness of ketorolac administration (30 mg i.v.) before a surgical operation in terms of postoperative analgesia improvement; 2) To evaluate the impact of preoperative ketorolac administration on perioperative renal function and on intraoperative water balance; 3) to evaluate the presence of adverse effect due to preoperative NSAID use.\n Prospective randomized trial.\n University surgical department.\n Forty adult patients undergoing major abdominal surgery, randomized in 2 groups: in group 1 ketorolac (30 mg i.v.) was administered immediately after the induction and, for postoperative analgesia, ketorolac (30 mg i.v.) was administered beginning at the time of skin closure; in group 2 no ketorolac was administered before the operation and postoperative treatment was the same. Buprenorphine (0.3 mg i.m.) was administered in case of unsatisfactory analgesia. Fluids infused and diuresis were measured intraoperatively. One, 6 and 24 hours after the end of operation pain was evaluated using pain intensity score and VAS. The day after the operation serum creatinine and urea were measured.\n No statistically significant differences were found between groups regarding fluids infused, intraoperative diuresis, postoperative pain, adverse effects and number of bleeding episodes. More than 50% of patients, in either groups, required opioids administration.\n Ketorolac (30 mg i.v.) administration before a major abdominal operation does not improve postoperative analgesia nor determines significant alterations in renal function or increase in the frequency of abnormal bleedings. Opiate administration is necessary in more than 50% of the patients to achieve adequate analgesia.", "Non-steroidal anti-inflammatory drugs (NSAIDs) are used as analgesic in postoperative pain to reduce opioid side effects, such as drowsiness and nausea. However, NSAIDs have not been used extensively in cardiac surgical patients due to the fear of untoward effects on gastric, renal, and coagulation parameters. This study will evaluate the efficacy and safety of three NSAIDs for pain control in CABG patients.\n One hundred and twenty patients scheduled for elective CABG surgery were enrolled in randomized, double blind, controlled study. Standardized fast track cardiac anesthesia was used. One dose of drug (75 mg diclofenac, 100 mg ketoprofen, 100 mg indomethacin, or placebo) was given pr one hour before tracheal extubation and a second dose 12 hr later. Pain was treated with morphine iv and acetaminophen po. Visual analogue pain scores were recorded at baseline, 3, 6, 12 and 24 hr after the first dose of drug.\n There were no differences among the groups in pain scores. Only patients who received diclofenac required less morphine than patients in the control group (P < 0.05). When the total amounts of pain medications were computed to morphine equivalents, only patients in the diclofenac group received less pain medications than the placebo group (P < 0.05). Proportion of patients with postoperative increase of creatinine level (20% and over) did not differ between placebo and drug groups.\n Non-steroidal anti-inflammatory drugs may be used for analgesia management post CABG surgery in selected patients. Diclofenac appears to have the best analgesic effects by reducing the morphine and other analgesic requirement postoperatively.", "This prospective, randomized study assessed the effect of dopamine on renal tubular function in patients who had coronary artery bypass grafting.\n Two groups of patients with normal preoperative renal function were randomly divided into a dopamine group (n=11), who received dopamine in a dose of 2 mg/kg x min, and a control group (n=11), who received no treatment. Dopamine infusion was initiated 24 hours before the operation and was continued for 48 hours postoperatively. Measurements of renal function obtained 2 days before the operation were considered preoperative and were repeated on the 1st, 3rd, and 7th postoperative days. Urinary excretion of b2-Microglobulin (b2-M), considered a sensitive means for diagnosing proximal tubular damage, was measured during the early (day 3) and late (day 7) postoperative period.\n There were no significant differences respect to the clearances of creatinine, osmotic, and free-water in the dopamine group compared with the control group (p>0.05). Urine microalbumin levels significantly increased on postoperative day 3 in both groups. During the early postoperative period, excretion of urine b2-M was significantly greater in the dopamine group than in the control group (p<0.05).\n Consequently, in patients with normal preoperative renal and cardiac function scheduled for elective coronary artery bypass grafting, renal dose dopamine infusion alone may not provide sufficient protection on tubular function and increases renal tubular injury during the early postoperative period.", "The aim of this study was to investigate whether steroid administration would increase the risk of postoperative infection. Sixty adults who underwent elective cardiac surgery under cardiopulmonary bypass were prospectively randomized into two groups. Thirty-one patients received hydrocortisone (50 mg x kg(-1)) before and after cardiopulmonary bypass, the other 29 served as controls. Various hemodynamic and pulmonary measurements were obtained perioperatively, and the white blood cell counts and levels of C-reactive protein were checked up to the 14(th) postoperative day. Steroid administration did not have any favorable effects during the perioperative period. Re-administration of antibiotics was needed in 7 patients (22.6%) after the 7(th) postoperative day in the steroid group, and in 3 (10.3%) in the control group. The peak white cell counts and C-reactive protein levels after the 7(th) postoperative day were significantly higher in the steroid group. Steroid administration offered no clinical benefit to patients undergoing cardiac surgery with cardiopulmonary bypass, and it may encourage minor infections in the late postoperative period." ]

[ "8782340", "12744870", "14575762", "11734734", "1557929", "2975452", "9323616", "1995721", "2172394" ]

[ "The quest for trials on the efficacy of human vaccines. Results of the handsearch of Vaccine.", "Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi children 18-36 months of age.", "Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine.", "Prospective, randomized, placebo-controlled evaluation of the safety and immunogenicity of three lots of intranasal trivalent influenza vaccine among young children.", "A randomized phase II study of a new tick-borne encephalitis vaccine using three different doses and two immunization regimens.", "[Characteristics of the clinical and immunologic safety of inactivated influenza vaccines in children undergoing multiple immunizations].", "Phase 1 trial of a candidate rotavirus vaccine (RV3) derived from a human neonate.", "A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population.", "Evaluation of WC3 rotavirus vaccine and correlates of protection in healthy infants." ]

[ "We report the results of the handsearch of all the issues of Vaccine from 1983 to 1994 to identify randomized and controlled clinical trials (RCTs and CCTs) with the aim of setting up a Cochrane data base of vaccine trials. We read 1119 original papers and located 231 trials of which 117 (50.6%) were RCTs and 114 (49.4%) were CCTs. This compared with a MEDLINE search yield of only 60 trials (25.9% of reports identified by handsearching). Hepatitis B vaccine was the most popular topic (25.5% of trial reports), followed by influenza (13.4% of trial reports) and Hepatitis A (10.4% of trial reports). Seventy per cent of trials had been carried out in Europe or North America and mean overall trial size was 1136 patients (median 110). Overall only 20 trial reports mentioned placebo explicitly, while 22 reports contained data on both overall and arm size which could not be reconciled. Reviewers of vaccine trials should not base searches exclusively on MEDLINE as they are likely to miss up to 75% of trial reports. Vaccine should adopt a standardized format of reporting of trials and contributors should conform to these rules.", "A phase II safety and immunogenicity study of an oral-formalin inactivated enterotoxigenic Escherichia coli (ETEC) vaccine containing six colonization factors (CFA/I, CS1, CS2, CS3, CS4, CS5) and 1mg of recombinant cholera toxin B subunit (the CF-BS-ETEC vaccine) was carried out in an urban slum of Dhaka city in Bangladesh. The study was carried out in a double blinded, placebo controlled design in 158 children, 18-36 months of age. Children were given two doses of the CF-BS-ETEC vaccine or the placebo which consisted of E. coli K12. The vaccine was well tolerated. The immune response was studied in 60 children (30 each in the placebo and vaccine group). Significant vaccine specific IgA antibody-secreting cell (ASC) responses were seen 7 days after ingestion of the first and second dose of the vaccine. The responses to CFA/I (P<or=0.001), CS2 (P=0.021), CS4 (P=0.009) and rCTB (P<or=0.001) were elevated in the vaccines in comparison to the pre-immune values and in comparison to those seen in the placebo recipients (P=0.018 to <0.001). Vaccines but not placebo recipients also showed significantly increased IgM ASC responses to all three CF antigens that were tested (P=0.012 to <0.001) and IgG-ASCs to rCTB (P<0.001). Peak ASC levels were reached after one dose of the vaccine with no further increase or decrease after the second dose. The vaccine recipients also responded with IgA plasma antibodies to CFA/I, CS1, CS2, CS4 and rCTB after one or two doses of the vaccine (P=0.01 to <0.001). Subjects in the placebo group failed to mount responses to any of the antigens. The vaccine also induced responses in mucosal IgA antibodies in feces to CFA/I, CS2 and rCTB (61, 88 and 69% responder frequency, respectively) and the magnitude of the response was elevated in comparison to the pre-immune levels (P=0.031 to <0.001) and to the levels of the control group (P=0.003 to <0.001). This study thus shows that the CF-BS-ETEC vaccine is well tolerated in children, 18-36 months of age and gives rise to significant systemic and mucosal IgA antibody responses.", "The safety and effectiveness of a Vero cell-derived inactivated Japanese encephalitis (JE) vaccine were compared with those of a current JE vaccine in non-clinical studies and a phase I clinical trial. The single-dose toxicity study showed no toxicity of either the current JE vaccine or the investigational Vero cell-derived JE vaccine. In a local irritation study, the degree of irritation caused by both vaccines was determined to be the same as that induced by normal saline. To investigate genotoxicity, a chromosomal aberration test was conducted and the results were negative. Both JE vaccines were administered to a group of 30 subjects who were seronegative (neutralizing antibody titer <10(1)) for JEV virus (Beijing-1 Strain). Each subject was subcutaneously inoculated twice at an interval of 1-4 weeks, followed by an additional booster inoculation 4-8 weeks later, and clinical reactions and serological responses were subsequently investigated. Adverse drug reactions of local reaction, headache and malaise were mild, occurring at a rate of 6.7 and 20.0% after administration of the Vero cell-derived JE vaccine and the current JE vaccine, respectively. The seroconversion rate after three doses of both JE vaccines was 100%, while the geometric mean titer for the Vero cell-derived and current JE vaccines was 10(2.35) and 10(2.03), respectively. These results suggest that the safety and effectiveness of the Vero cell-derived inactivated JE vaccine are equal to those of the currently available conventional vaccine in humans, and that the Vero cell-derived vaccine could be a useful second-generation JE vaccine.", "Trivalent formulations of an experimental, cold-adapted, intranasal influenza (CAIV) vaccine have been shown to be safe, immunogenic and efficacious in young children.\n We evaluated the safety and immunogenicity of three consistency lots of CAIV in children 12 to 36 months of age randomized to one of five groups: Groups 1, 2 and 3 received separate lots containing A/Shenzhen/227/95 (H1N1), A/Wuhan/359/95(H3N2) and B/Harbin/7/94-like viral strains. Group 4 received an earlier efficacy trial lot which included a different H1N1 strain (A/Texas/36/91-like); and Group 5 received placebo. We performed strain-specific serum hemagglutination inhibition antibody levels against type A (H3N2 or H1N1) or type B as appropriate.\n Overall 474 children received 2 doses, 2 months apart. Each lot was well-tolerated, and there were no significant group differences between consistency lots in the proportion of children with fever and local or systemic reactions after vaccination. The 3 consistency lots were not statistically different with regard to immunogenicity as measured by seroconversion or absolute geometric mean titer. Immune responses were more robust among initially seronegative children and for H3N2 and B strains than for H1N1 strains. After 2 doses of vaccine 97, 84 and 62% had hemagglutination inhibition titers > or = 1/32 against A/H3N2, B and H1N1 strains, respectively. For A/H3N2 only, immune responses after 1 dose of vaccine are similar to those seen after 2 doses.\n Each consistency lot of CAIV is as or more immunogenic than a lot used in a large efficacy trial.", "A new, highly purified inactivated tick-borne encephalitis (TBE) vaccine (FSME-Vaccine Behring, BI 71.061) was recently registered in Germany. A multinational phase II study was performed in seven centres located in areas endemic for TBE. A total of 379 healthy adults were randomly allocated into three dosage groups (1.0, 1.5 and 2.0 micrograms antigen per dose, respectively) and into two immunization schedules [vaccination with one dose of 0.5 ml intramuscularly on days 0, 7 and 21 (abbreviated schedule), or on days 0, 28 and 300 (conventional schedule)]. Antibody response to vaccination was assayed by enzyme-linked immunosorbent assay (ELISA), haemagglutination inhibition test (HIT) and neutralization test (NT). Seroconversion rates in the different groups 28 days after one single dose were 75.3-83.5% in ELISA, 35.8-50.6% in HIT, and 100% in NT. All vaccinees showed seroconversion in all tests on day 42 in the conventional schedule and on day 35 in the abbreviated schedule, with the exception of one subject, who remained seronegative in HIT only. Geometric mean titres (GMT) of about 3000 in ELISA were achieved by two vaccinations in the conventional schedule and showed a booster increase to 5500-8000 GMT after revaccination on day 300. Overall frequency of adverse events (related and unrelated) was 37% (conventional schedule) and 46% (abbreviated schedule) after the first, 9% and 21% after the second, and 5% and 15% after the third vaccination, respectively. Generally, side effects were mild and transient, including mainly headache, fever, malaise and local irritation. Serious, vaccine-related side effects did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a strictly controlled epidemiological trial on 12,643 school children aged 11-14 years the reactogenic properties and safety of killed influenza chromatographic vaccine under the conditions of multiple immunization were studied. A single immunization dose of the vaccine (0.2 ml) contained the hemagglutinins of influenza viruses A/Philippines/82 (H3N3) and A/Kiev/59/79 (H1N1), 3.5 micrograms each. The preparation was introduced by means of a jet injector. The vaccine was shown to be clinically and immunologically safe under the conditions of the regular multiple immunization of children over the period of 4 years.", "To conduct a phase 1 safety and tolerability trial of an oral rotavirus vaccine candidate RV3 in healthy volunteers.\n Double blind placebo controlled trial of a single 1 mL oral dose (6.5 x 10(5) fluorescing focus units [FFU]/mL) in 10 healthy young men, 10 3-4 year old children and 10 3 month old infants with a 4 week surveillance period. The study was undertaken at a children's hospital and nearby community in Melbourne, Australia.\n All subjects successfully completed the trial. There were no significant side-effects attributable to the vaccine preparation in any age group. No shedding of vaccine virus was detected by enzyme immunoassay. There was evidence of an immune response in serum and/or gut secretions in two of five vaccinees in each age group.\n RV3 rotavirus vaccine appears to be safe and well tolerated. Evidence of immunogenicity in some subjects after a single dose encourages further trials to determine immunogenicity after three doses, after reduction of viral dose, and without prior administration of buffer.", "A double-blind, randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and RIT 4237, a bovine rotavirus vaccine, in a Navajo population. Infants aged 2-5 months were randomized to receive one dose of either 10(4) pfu of the rhesus rotavirus vaccine or 10(8) pfu of the RIT 4237 vaccine or placebo. Eleven (10.2%) of 108 infants in the rhesus vaccine group, 11 (10.4%) of 106 in the RIT 4237 group, and 9 (8.4%) of 107 in the placebo group experienced rotavirus diarrhea during the follow-up period of 17 months. Thus, in this population, neither vaccine was efficacious in preventing rotavirus diarrhea.", "The safety, immunogenicity, and efficacy of WC3 rotavirus vaccine was evaluated in a double-blind, placebo-controlled trial of healthy infants 2-12 months of age; 103 received one dose of vaccine and 103 received placebo. Vaccination appeared to be safe and induced an antibody response (WC3 neutralizing antibody) in 97% of vaccinees. Only 9 (9%) of these, however, produced antibody to human rotavirus serotypes; at least 7 of the 9 were naturally infected before vaccination. Neither the number of symptomatic episodes of rotavirus diarrhea (21 vs 25) nor the number of moderate to severe rotavirus illnesses (9 vs. 15) was significantly different in vaccine or placebo recipients, respectively, during a predominantly serotype 1 rotavirus season. A slight but significant decrease in mean symptom score was detected in vaccine recipients. Despite an overall lack of efficacy, protection could be correlated to previous rotavirus infection, high levels of WC3 neutralizing antibody, and preexisting (maternal) serotype 1 neutralizing antibody with a titer greater than or equal to 30." ]

[ "1537158", "18608367", "1512910", "20142693", "1471839", "2743665", "9007770", "18442423", "3430154" ]

[ "The influence of continuous passive motion on the results of total knee arthroplasty.", "Continuous passive motion as an adjunct to active exercises in early rehabilitation following total knee arthroplasty - a randomized controlled trial.", "A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty.", "Use of inpatient continuous passive motion versus no CPM in computer-assisted total knee arthroplasty.", "Beneficial effects of continuous passive motion after total condylar knee arthroplasty.", "Continuous passive motion versus physical therapy in total knee arthroplasty.", "The effect of continuous passive motion duration and increment on range of motion in total knee arthroplasty patients.", "Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.", "Continuous passive motion after total knee arthroplasty." ]

[ "Twenty-two primary total knee arthroplasties were prospectively randomized into one of two treatment protocols. Ten of these patients were managed in the hospital after surgery by means of a postoperative splint. The remaining 12 patients were placed immediately postoperatively in the recovery room into the continuous passive motion (CPM) device. The study compares the range of motion, analgesic use, hospital stay, and the volume of hemovac output in the two groups. These cases demonstrated two statistically significant findings with the use of CPM: (1) decreased use of narcotic analgesics and (2) decreased length of hospital stay.", "Continuous passive motion is frequently used post-operatively to increase knee range of motion after total knee arthroplasty in spite of little conclusive evidence. The aim of this study was to examine whether continuous passive motion (CPM) as an adjunct to active exercises had any short time effects (after one week and three months) on pain, range of motion, timed walking and stair climbing.\n A randomized controlled trial was conducted. A total of 63 patients undergoing primary TKA were randomly assigned into an experimental group receiving CPM and active exercises and a control group receiving active exercises only. Outcomes were assessed by goniometer, visual analogue scale (VAS), timed 'Up and Go' test (TUG), timed 40 m walking distance and timed stair climbing.\n There were no statistical differences between the treatment groups for any outcome measures either at one week or after three months. For the whole group, a significant and 50% reduction in pain score was found after three months (p < 0.01). Compared with before surgery, a significantly impaired knee flexion range of motion (p < 0.01) and a significantly decreased number of patients able to climb stairs were found after three months (p < 0.01).\n CPM was not found to have an additional short-time effect compared with active physiotherapy. After three months considerable pain relief was obtained for the whole group, the patients preoperative ROM was not restored and the number of patients able to climb stairs had decreased.", "To evaluate the efficacy of continuous passive motion (CPM) in the postoperative management of patients undergoing total knee arthroplasty.\n A randomized controlled single-blind trial of CPM plus standardized rehabilitation vs standard rehabilitation alone.\n A referral hospital for arthritis and musculoskeletal care.\n Consecutive patients with end-stage osteoarthritis or rheumatoid arthritis undergoing primary total knee arthroplasty who had at least 90 degrees of passive knee flexion. One hundred fifty-four patients were eligible and 102 patients agreed to participate and were randomized. Ninety-three patients completed the study protocol.\n Continuous passive motion machines programmed for rate and specified arc of motion within 24 hours of surgery with range increased daily as tolerated with standardized rehabilitation program compared with standardized rehabilitation program alone.\n Primary outcomes were pain, active and passive knee range of motion, swelling (or circumference), quadriceps strength at postoperative day 7, as well as complications, length of stay, and active and passive range of motion and function at 6 weeks.\n Use of CPM increased active flexion and decreased swelling and the need for manipulations but did not significantly affect pain, active and passive extension, quadriceps strength, or length of hospital stay. At 6 weeks there were no differences between the two groups in either range of motion or function. In this series, use of CPM resulted in a net savings of $6764 over conventional rehabilitation in achieving these results.\n For the average patient undergoing total knee arthroplasty, CPM is more effective in improving range of motion, decreasing swelling, and reducing the need for manipulation than is conventional therapy and lowers cost.", "Continuous passive motion (CPM) has shown positive effects on tissue healing, edema, hemarthrosis, and joint function (L. Brosseau et al., 2004). CPM has also been shown to increase short-term early flexion and decrease length of stay (LOS) ( L. Brosseau et al., 2004; C. M. Chiarello, C. M. S. Gundersen, & T. O'Halloran, 2004). The benefits of CPM for the population of patients undergoing computer-assisted total knee arthroplasty (TKA) have not been examined.\n The primary objective of this study was to determine whether the use of CPM following computer-assisted TKA resulted in differences in range of motion, edema/drainage, functional ability, and pain.\n This was an experimental, prospective, randomized study of patients undergoing unilateral, computer-assisted TKA. The experimental group received CPM thrice daily and physical therapy (PT) twice daily during their hospitalization. The control group received PT twice daily and no CPM during the hospital stay. Both groups received PT after discharge. Measurement included Knee Society scores, Western Ontario McMaster Osteoarthritis Index values, range of motion, knee circumference, and HemoVac drainage. Data were collected at various intervals from preoperatively through 3 months.\n Although the control group was found to be higher functioning preoperatively, there was no statistically significant difference in flexion, edema or drainage, function, or pain between groups through the 3-month study period.", "A randomised, controlled study of the use of postoperative continuous passive motion (CPM) and immobilisation regimen after total condylar knee arthroplasty was performed. CPM resulted in a significant increase in both the early and late range of knee flexion. This increase occurred in both rheumatoid and osteoarthritic patients. The improvement of 10 degrees at 12 months allowed additional important function to be attained. CPM resulted in significantly earlier discharge from hospital. It did not increase the clinical incidence of wound healing problems, nor did it significantly increase the postoperative fixed flexion deformity or the extension lag. CPM can be recommended as a safe and effective modality to achieve more rapid and more successful postoperative rehabilitation after knee arthroplasty.", "To determine the justification of a continuous passive motion machine in the treatment of postoperative total knee arthroplasties, a comparative study of 50 consecutive patients with simultaneous bilateral total knee arthroplasties was undertaken. The patients served as their own controls because one randomly selected knee was placed in the machine while the remaining knee was treated with physical therapy only. There was no significant difference in the range of motion during the eight days of hospitalization or the follow-up visits at two weeks, two months, six months, and one year. There was a significant decrease in the swelling about the knee. The continuous passive motion treated knees appeared to be generally weaker as revealed by more extensor lags and flexor tightness at discharge from the hospital. Also, increased costs incurred from the need for additional equipment and increased staff time made the machine neither cost-effective nor beneficial.", "There is insufficient information on continuous passive motion (CPM) parameters in total knee arthroplasty patients for optimal patient outcomes. We compared CPM duration and increments on active and passive range of motion (ROM) in patients who underwent a unilateral total knee arthroplasty due to degenerative joint disease. Forty-five total knee arthroplasty patients were randomly assigned to either a control group, a short CPM duration (3-5 hours per day) group with CPM ROM increased 5 degrees twice daily, a short CPM duration group with CPM ROM increased daily to patient tolerance, a long CPM duration (10-12 hours per day) group with CPM ROM increased 5 degrees twice daily, or a long CPM duration group with CPM ROM increased daily to patient tolerance. Active and passive flexion and extension were measured goniometrically on each postoperative day that the patient was treated by physical therapy. No statistically significant differences between groups were found for baseline and final postoperative ROM. The CPM groups did not maintain the parameters assigned and were combined, revealing an enhanced rate of change of flexion. Most patients opted for a CPM duration of between 4 and 8 hours per day and the patient-preferred CPM incremental increase in ROM was 6-7 degrees/day.", "Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered.\n In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee.\n Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments.\n Although results indicate that prolonged CPM use might have a small short-term effect on RoM, routine use of prolonged CPM in patients with limited RoM at hospital discharge should be reconsidered, since neither long-term effects nor transfer to better functional performance was detected.\n ISRCTN85759656.", "Sixty-two patients undergoing primary total knee arthroplasty were studied prospectively. There were 42 patients in whom continuous passive motion (CPM) was used after surgery and 20 controls. The two groups were comparable with respect to age, diagnosis, sex, weight, and preoperative deformity and motion. The mean length of time required for CPM patients to achieve 90 degrees of flexion (9.1 days) was shorter than that for the control group (13.8 days). At the time of discharge from the hospital, however, there was no significant difference between the groups in amount of either flexion or extension. All patients had venograms performed after arthroplasty; the incidence of positive studies indicating thrombophlebitis was 45% in CPM patients and 75% in controls. These data demonstrate that CPM after knee arthroplasty enables patients to recover motion more quickly and affords some protection against deep vein thrombosis." ]

[ "1889273", "12379544", "3063043", "3033040", "6998390", "11500337", "2194417", "3324594", "10021717" ]

[ "Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen.", "Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial.", "Failure of topically applied antibiotics, added to systemic prophylaxis, to reduce perineal wound infection in abdominoperineal excision of the rectum.", "Prevention of colonization and respiratory infections in long-term ventilated patients by local antimicrobial prophylaxis.", "Prophylactic antibiotics in vascular surgery. Topical, systemic, or both?", "Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study.", "Antibiotics in elective colon surgery. A randomized trial of oral, systemic, and oral/systemic antibiotics for prophylaxis.", "Single-dose v. short-term antibiotic therapy for prevention of wound infection in general surgery. A prospective, randomized double-blind trial.", "Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial." ]

[ "The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation.", "We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and stratified according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 x 400 mg of intravenous ciprofloxacin for 4 days, together with a mixture of topical gentamicin and polymyxin applied to the nostrils, mouth, and stomach throughout their ICU stay or to receive intravenous and topical placebo. When receiving prophylaxis, significantly fewer patients acquired infections (p = 0.001, risk ratio [RR], 0.477; 95% confidence interval [CI], 0.367-0.620), especially pneumonias (6 versus 29, p = 0.007), other lower respiratory tract infections (39 versus 70, p = 0.007), bloodstream infections (14 versus 36, p = 0.007), or urinary tract infections (36 versus 60, p = 0.042). Also, significantly fewer patients acquired severe organ dysfunctions (63 versus 96 patients, p = 0.0051; RR, 0.636; 95% CI, 0.463-0.874), especially renal dysfunctions (17 versus 38; p = 0.018). Within 5 days after admission, 24 patients died in each group, whereas 28 patients receiving prophylaxis and 51 receiving placebo died in the ICU thereafter (p = 0.0589; RR, 0.640; 95% CI, 0.402-1.017). The overall ICU mortality was not statistically different (52 versus 75 fatalities), but the mortality was significantly reduced for 237 patients of the midrange stratum with APACHE-II scores of 20-29 on admission (20 versus 38 fatalities, p = 0.0147; RR, 0.508; 95% CI, 0.295-0.875); there was still a favorable trend after 1 year (51 versus 60 fatalities; p = 0.0844; RR, 0.720; 95% CI, 0.496-1.046). Surveillance cultures from tracheobronchial, oropharyngeal, and gastric secretions and from rectal swabs did not show any evidence for the selection of resistant microorganisms in the patients receiving prophylaxis.", "In a prospective, randomized trial, prophylactic use of topical antibiotics in addition to systemic prophylaxis was studied in patients undergoing abdominoperineal amputation of the rectum. All patients received gentamicin 80 mg and metronidazole 500 mg intravenously at induction of anesthesia, followed by the same dose 8 hourly for 48 hours. In accordance with the randomization, half of the patients were additionally given gentamicin 160 mg + metronidazole 400 mg topically into the perineal wound at closure. Perineal wound infection appeared in 19 of the 41 patients who received both systemic and topical prophylaxis, and in 18 of the 38 with only systemic antibiotics. Cell-mediated immunity was preoperatively assessed with a skin test (Multitest) in all but three patients. Impairment of cell-mediated immunity was associated with significantly heightened rate of wound infection, and these patients did not benefit from topical antibiotics.", "In a randomized clinical trial the prophylactic effects of locally administered antimicrobials on quantitative colonization and respiratory infections were studied in intubated patients with an expected period of mechanical ventilation of greater than 6 days. Nineteen patients received 50 mg of polymyxin B and 80 mg of gentamicin distributed among nose, oropharynx and stomach at 6-h intervals, as well as 300 mg of amphotericin B in the oropharynx. Twenty untreated patients served as controls. In the control group colonization by respiratory pathogens was more common (oropharynx 19 vs 6 patients (p less than 0.001); trachea 19 vs 11 (p less than 0.01)), and the number as well as the count of the colonizing species was usually higher. Fourteen patients of the control group developed respiratory infections, including nine cases of pneumonia, as compared to four patients with prophylaxis, including one case of pneumonia (p less than 0.01). Pneumonia-associated deaths were prevented with prophylaxis; however, the overall mortality remained unchanged. Respiratory infections in the prophylaxis group were associated with organisms resistant to the agents used, but the overall occurrence of resistance was not increased, as compared to the control group. We conclude that unrestrained upper airway colonization by respiratory pathogens and respiratory tract infection were causally related. Local antimicrobial prophylaxis proved to be a highly effective strategy for the prevention of potentially life-threatening pneumonias in critically ill patients, but in the present study the host setting appeared to be the major determinant of outcome.", "A prospective, randomized, blinded study was performed to determine whether prophylactic antibiotics would reduce the incidence of infection in peripheral vascular surgery and whether the route of antibiotic administration was important. Patients undergoing a vascular procedure with a groin incision were allocated to one of four groups with respect to prophylactic antibiotics. Group I received no antibiotic. Group II had topical cephradine instilled in their incisions prior to closure. Group III received a 24-hour perioperative course of intravenous cephradine, and Group IV received both topical and intravenous cephradine. Groin and abdominal incisional infections were significantly reduced (p < 0.01) among patients who received prophylactic antibiotics by either the topical, systemic, or combined routes of administration. No significant differences were noted among the three antibiotic groups. Profundoplasty, femoral embolectomy, and femoral aneurysm repair were each associated with an increased incidence of infection (p < 0.01). Other risk factors were only important in patients not receiving antibiotics. Either intraoperative topical antibiotics or perioperative systemic antibiotics prevent infection in peripheral vascular surgery, but antibiotic administration by both routes is unnecessary.", "Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated. Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis. In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis [control group A] and 61 patients were studied in an intensive care unit where no topical prophylaxis was used [control group B]). Baseline characteristics were comparable in all three groups. Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A [p < 0.00001] and 9% in control group B patients [p < 0.00001]) and in trachea (52% versus 22% in A [p = 0.03] and 7% in B [p = 0.004]). Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A [p < 0.00001] and 63% in B [p < 0.00001]). Colonization rates in stomach and intestine were not affected. Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively). This was not associated with shorter durations of ventilation or ICU stay or better survival. Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention. Keywords: cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects", "A prospective, randomized double-blind study was undertaken to compare the efficacy of three prophylactic regimens (oral neomycin and erythromycin, intravenous cefoxitin, and a combination of both oral and intravenous antibiotics) in patients undergoing elective colorectal surgery. One hundred sixty-nine patients were randomized and 146 patients were evaluable. Septic complications occurred in 11.4 per cent of patients receiving oral antibiotics only, in 11.7 per cent of patients receiving intravenous cefoxitin alone, and in 7.8 per cent of patients receiving both oral and intravenous antibiotics. These differences were not statistically different. The greatest number of septic complications occurred in those patients with anastomotic disruptions. Two patients died (1.3%), both of whom had major anastomotic failures. There was no advantage between any of the groups in the incidence of wound infection (3.9-6.8%). Thus, no advantage could be identified in this study in the combination of oral and intravenous antibiotics in elective colorectal surgery.", "To investigate the effectiveness of a single-dose antibiotic regimen for preventing postoperative wound infection, a prospective, randomized double-blind trial was carried out in patients undergoing \"clean-contaminated\", \"contaminated\" or \"clean\" (vascular) surgery. Both elective and emergency operations were included. Single-dose (preoperative) prophylaxis was compared with short-term prophylaxis (1 dose preoperatively and 2 doses postoperatively). The antibiotics were penicillin, tobramycin and metronidazole in various combinations, and comparisons between single-dose and short-term prophylaxis were made with all the regimens. The incidence of wound infection was 5/277 (1.8%) in the short-term group and 9/287 (3.1%) in the single-dose group. The difference was not statistically significant. Nor was statistically significant difference found when the type of operation and the degree of contamination were considered. Single-dose antibiotic prophylaxis thus gave a low incidence of postoperative wound infection, even in \"clean-contaminated\" or \"contaminated\" cases.", "To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS.\n Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required.\n Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls.\n Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies." ]

[ "11806295", "7954233", "12515103", "19092335", "16710858", "11896097", "18424367", "12143204", "11286304" ]

[ "[Trimetazidine prevents ischemia-reperfusion injury in hepatic surgery under vascular clamping].", "Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial.", "[Coronary artery disease observed in general hospitals: ETTIC study. Comparison between trimetazidine and mononitrate isosorbide for patients receiving betablockers].", "A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic.", "Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: a prospective randomized study.", "Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study.", "Ischemic preconditioning improves postoperative outcome after liver resections: a randomized controlled study.", "The role of allopurinol in human liver ischemia/reperfusion injury: a prospective randomized clinical trial.", "Anti-ischaemic efficacy and tolerability of trimetazidine administered to patients with angina pectoris: results of three studies." ]

[ "Clamping the hepatic pedicle (or Pringle's manoeuvre) is frequently used to reduce blood loss during liver surgery. This induces a normothermic ischaemia of the overall liver. In this study we have investigated the anti-ischaemic effect of trimetazidine during surgery on hydatid cysts of the liver requiring vascular clamping of the hepatic pedicle. Seventy-six hepatic pericystectomies were performed under a 40 min normothermic ischaemia. Two randomized groups including 38 patients each received daily either trimetazidine (80 mg/kg, group 1) or placebo (group 2) for 5 days before surgery. The effect of trimetazidine was evaluated on different parameters, the macroscopic appearance of the tissue, the ATP content in liver biopsies obtained before and after 15, 30 and 60 min reperfusion, the activity of the aminotransferase in the plasma and the plasma concentrations of reduced and oxidized gluthatione. No mortality was observed. The duration of hospital stay was reduced for patients treated with trimetazidine (8 +/- 1 days compared with 11 +/- 1.5 days for patients in group 2; p < 0.05). Morbidity rate was lower in group 1 (11 per cent) than in group 2 (18.5 per cent) but the decrease was not significant. Trimetazidine treatment reduced cytolysis (p < 0.05 on day 1, day 3, day 5), increased liver ATP content and limited the increase of reduced and oxidized gluthatione in the plasma during reperfusion. These results suggest that trimetazidine alleviates ischaemia-reperfusion injury during liver surgery and may allow extension of the ischaemic period without damage to the liver.", "Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer.\n Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations.\n The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month).\n This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials.", "The extended use of interventional surgery of revascularisation has modified the prognosis and the evolution of ischaemic heart diseases. However, both coronary artery bypass graft and percutaneous transluminal coronary angioplasty failed to make the symptomatic or subclinical ischaemic manifestations of chronic coronary insufficiency disappear. The interest of using betablockers as a first-line therapy was widely demonstrated. However, their combination with another efficient molecule is often necessary. The aim of this trial has been to appreciate the efficiency of the association of a betablocker with either trimetazidine or with isosorbide monoitrate. Hundred and eighty five patients retaining a positive effort test despite 100 mg of atenolol, received in addition, either 60 mg of trimetazidine (93 cases) of 60 mg of isosorbide mononitrate (92 cases) for a two-month period and are then re-evaluated at the end of this period. The ischaemic threshold is delayed in a significant way in both groups (p < 0.0001; trimetazidine +7%, isosorbide mononitrate +10.7%). Twenty-three percent of the exercise tests under trimetzidine and 19% under isosorbide mononitrate become negative after two months of the therapeutic combination. The clinical improvement is even clearer with the disappearance of the angina crisis during the week before the second exercise test in 63% of the cases under trimetazidine and 54% of the cases under isosorbide mononitrate, among the patients who had kept it under atenolol at the inclusion. In conclusion, the combination of a second efficient molecule, trimetazidine or isosorbide mononitrate, brings a functional and objective improvement to patients with insufficient chronic coronary disease not totally controlled using a betablocker, even with high dosage. One should notice two important advantages in favour of the trimetazidine: one is practical due to a better tolerance (lack of cephalalgia), the other is conceptual (use of the complementary metabolic approach of cellular oxygenation rather than the haemodynamic approach of nitrate compounds which are already in concurrency with all other anti-ischaemic molecules).", "To evaluate the effects of pharmacological preconditioning with a volatile anesthetic in patients undergoing liver resection with inflow occlusion.\n In liver surgery, ischemic preconditioning and intermittent clamping are the only established protective strategies to reduce tissue damage due to ischemia during inflow occlusion. Preconditioning with volatile anesthetics has provided protection against cardiac and renal ischemic injury in several animal models through NO and HO-1 pathways. But pharmacological preconditioning has never been tested in patients undergoing liver surgery in a randomized trial.\n Sixty-four patients undergoing liver surgery with inflow occlusion were randomized intraoperatively for preconditioning with sevoflurane or not (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with propofol. Thirty minutes before inflow occlusion propofol was replaced by sevoflurane in the preconditioning group. Primary endpoint was postoperative liver injury assessed by peak values of liver transaminases. Postoperative complications were recorded according to an established scoring system.\n Sevoflurane preconditioning significantly limited the postoperative increase of serum transaminase levels by 261 U/L (95% CI, 65 to 458; P = 0.01) for the ALT and by 239 (95% CI, -2 to 480; P = 0.05) for the AST corresponding to decreases of baseline levels of 35% and 31%, respectively. Patients with steatosis had an even better benefit than patients without steatosis. The rates of any complication (risk ratio 0.46; 95% CI, 0.25 to 0.85; P = 0.006) and of severe complications requiring invasive procedures (risk ratio 0.25; 95% CI, 0.06 to 1.08; P = 0.05) were also lowered by preconditioning.\n This first randomized trial of pharmacological preconditioning in liver surgery in humans showed a protective effect of preconditioning with volatile anesthetics. This strategy may provide a new and easily applicable therapeutic option to protect the liver and to lower complication rates.", "Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response.", "Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated.\n Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival.\n The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P =.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P =.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P =.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P =.19)\n These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.", "Clamping of the portal triad (Pringle maneuver) prevents blood loss during liver resection, but leads to liver injury upon reperfusion. Ischemic preconditioning (IP) has been shown to protect the liver against prolonged ischemic injury in animal models. However, the clinical value of this procedure has not yet been established.\n 61 Patients undergoing hepatic resection under inflow occlusion were randomized to either to receive (Group-A n = 30) or not to receive (Group-B n = 31) an IP (10 minutes of ischemia followed 10 minutes of reperfusion).\n Mean (+/- SD)/ Group-A vs. Group-B. Pringle time of 34 +/- 14 and 33 +/- 12 minutes and the extent of resected liver tissue (2.7 +/- 1.3 vs. 2.7 +/- 1.1 segments) were comparable in both groups. Complications, including death, severe liver dysfunction and biliary leakage occurred in 6 patients of Group-A vs. 14 patients of Group-B (p<0.05). Intraoperative blood loss was significantly lower in Group-A (1.28 +/- 0.91 l vs. 1.94 +/- 0.76 l; p<0.001) with 5 vs. 15 patients requiring transfusions (p<0.01). In a multivariate analysis the duration of the Pringle maneuver (p<0.05) and the absence of preconditioning (p<0.05) were independent predictors for the occurrence of postoperative complications.\n IP protects against reperfusion injury, reduces the incidence of complications after hepatic resection under inflow occlusion and is simple to use in clinical practice.", "To investigate the effect of pretreatment with allopurinol on oxidative stress during reperfusion and the role in liver tissue protection in partial liver resections for colorectal cancer metastases confined to the liver.\n Prospective, randomized, clinical trial, single center, Leiden University Medical Center, The Netherlands.\n Curative partial liver resection of colorectal metastases in 16 patients with or without allopurinol pretreatment, between June 1992 and February 1994.\n Partial liver resections with Pringle maneuver, intravenous allopurinol versus no allopurinol.\n The effect of allopurinol on liver cell damage caused by ischemia/reperfusion studied by measuring malondialdehyde, glutathione, glutathione disulfide, vitamin C, liver enzymes and blood clotting factors in blood samples. Morbidity and mortality were also evaluated.\n Pretreatment with allopurinol had no significant effect on any of our study parameters.\n Because ischemia/reperfusion damage is little in our study, pretreatment with allopurinol is of no value.", "Several clinical studies have compared the anti-ischaemic properties of trimetazidine used as monotherapy with those of standard anti-anginal therapy. In the treatment of uncontrolled angina pectoris, the addition of a metabolic agent such as trimetazidine to existing therapy with a haemodynamic agent would appear to confer advantages over the addition of a second haemodynamic agent. Here we report the results of three studies conducted in Poland, the Czech Republic and Hungary that provide additional evidence for the beneficial effects of combining trimetazidine with a conventional haemodynamic agent such as beta-blockers, long-acting nitrate or calcium channel blockers. This combination provided significant benefits in terms of improved exercise capacity and decreased number of angina attacks along with a good tolerability profile." ]

[ "8625660", "11243949", "19863361", "9713447", "10343624", "15363007", "3514164", "10095821", "12583942" ]

[ "Effects of long-term treatment with corticosteroids in COPD.", "Systemic glucocorticoids in severe exacerbations of COPD.", "Effect of fluticasone propionate/salmeterol (250/50) on COPD exacerbations and impact on patient outcomes.", "Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease.", "Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis.", "Does addition of inhaled steroid to combined bronchodilator therapy affect health status in patients with COPD?", "Corticosteroids in COPD. A clinical trial and reassessment of the literature.", "The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease.", "Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial." ]

[ "To determine the effectiveness of treatment with corticosteroids in patients with COPD.\n In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 micrograms/d; inhaled budesonide, 1,600 micrograms/d, plus oral prednisolone, 5 micrograms/d (bud + pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject.\n Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the plac group (n = 5 out of 18) than in the actively treated groups (n = 2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV1 was 60 mL/yr in the plac group, 40 mL/yr in the bud + pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups.\n Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD.", "This study aimed to compare the efficacies of 3-day and 10-day courses of methylprednisolone (MP) treatment in severe COPD exacerbations necessitating hospitalization for respiratory failure.\n Prospective, randomized, single-blind study.\n Tertiary-care center.\n Thirty-six patients were included in the study and randomized into two groups: group 1 received MP, 0.5 mg/kg q6h for 3 days, and group 2 was administered the same dosage of MP for the first 3 days, after which it was tapered and terminated on the tenth day. There was no difference between the groups for age, baseline FEV(1), PaO(2), PaCO(2), and pH levels. One patient in group 1 who developed pneumothorax and one patient in group 2 who had steroid-related psychosis could not complete the study.\n Both groups showed significant improvements in PaO(2) and FEV(1) levels, but these were more marked in group 2 (p = 0.012 and p = 0.019, respectively). There was a significant increase in FVC levels in group 2 only (p = 0.003). Group 2 also had a more marked improvement in dyspnea on exertion. There was no difference between the two groups with regards to other parameters, including pH, PaCO(2) levels, and other symptom scores. Six patients in group 1 and five patients in group 2 developed new exacerbations within the following 6 months. Hyperglycemia occurred in two patients in each group.\n In severe COPD exacerbations, a 10-day course of steroid treatment is more effective than a 3-day course in improving the outcome, but has no benefit in reducing exacerbation rates.", "Prevention and treatment of COPD exacerbations are recognized as key goals in disease management. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/salmeterol 250 mcg/50 mcg (FSC 250/50) and salmeterol 50 mcg (SAL) twice-daily on moderate/severe exacerbations. Subjects received treatment with FSC 250/50 during a one month run-in, followed by randomization to FSC 250/50 or SAL for 52 weeks. Moderate/severe exacerbations were defined as worsening symptoms of COPD requiring antibiotics, oral corticosteroids and/or hospitalization. In 797 subjects with COPD (mean FEV(1) = 0.98L, 34% predicted normal), treatment with FSC 250/50 significantly reduced the annual rate of moderate/severe exacerbations by 30.4% compared with SAL (1.10 and 1.59 per subject per year, respectively, p < 0.001), the annual rate of exacerbations requiring oral corticosteroids by 34% (p < 0.001) and the annual rate of moderate/severe exacerbations requiring hospitalization by 36% (p = 0.043). Clinical improvements observed during run-in treatment with FSC 250/50 were better maintained over 52 weeks with FSC 250/50 compared to SAL. Statistically significant reductions in albuterol use, dyspnea scores, and nighttime awakenings and numerical benefits on quality of life were seen with FSC 250/50 compared with SAL. The incidence of adverse events was similar across groups. Pneumonia was reported more frequently with FSC 250/50 compared with SAL (7% vs. 2%). FSC 250/50 is more effective than SAL at reducing the rate of moderate/severe exacerbations. These data confirm the beneficial effect of FSC on the management of COPD exacerbations and support the use of FSC in patients with COPD.", "Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.\n In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.\n Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.\n Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD.", "The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: \"Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?\"\n A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with \"asthmatic features\" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 micrograms beclomethasone daily, six with 1600 micrograms budesonide daily, and eight with 800 micrograms beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated.\n No baseline differences were observed (mean age 61 years, mean FEV1 45% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group.\n This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.", "Withdrawal of corticosteroid is associated with a deterioration of health status in COPD. In this study the aim was to determine whether high dose inhaled corticosteroid improves quality of life in patients with COPD.\n In total, 38 male patients with moderate COPD were included in the study. Baseline quality of life scores were determined using a Turkish version of the St George's Respiratory Questionnaire (SGRQ). Patients were randomly divided into two groups. Group 1 consisted of 20 patients who received existing bronchodilator therapy plus inhaled corticosteroid (800 micro g budesonide) for 12 weeks, while 18 patients in group 2 received bronchodilator and placebo. The SGRQ was repeated after the treatment period.\n All patients were male and mean age was 67 +/- 8.2 years. Symptom, activity, impact, and total scores were assessed and a difference of four units with treatment was considered to be clinically significant. Total score and activity score were decreased by six units and eight units, respectively, in the placebo group while symptom and impact scores did not change significantly. Total scores and the three component scores improved significantly in the corticosteroid group compared to the placebo group (Deltatotal score: -22 in corticosteroid group, -6 in placebo group, P < 0.01).\n Inhaled corticosteroid improved quality of life scores in patients with COPD, without significant improvement in airflow obstruction parameters. Since improvement of health status is one of the important aims in COPD treatment, use of inhaled corticosteroids should be considered from this perspective.", "A placebo-controlled, double-blind cross-over trial was conducted to assess whether 16 men with chronic obstructive pulmonary disease (COPD) would benefit from orally taken corticosteroids. Two weeks of treatment with 40 mg of prednisone daily did not result in improvement of pulmonary symptoms or function in the group as a whole, although one patient had small improvement in airflow. The baseline spirometric data and beta-agonist responsiveness of the patients in the study were then compared to a reference population consisting of 264 men who fulfilled a criteria for chronic obstruction out of 730 men who comprised a systematic sample drawn from all patients referred for spirometry at three hospitals. Our study subjects and those of five similar trials of corticosteroids in COPD had more severe obstruction than this reference group. Furthermore, the proportion of steroid responders found in each study was inversely related to the baseline FEV1 of the patients examined. It appears that previous studies of corticosteroids in COPD may have overestimated the number of COPD patients who might benefit from corticosteroids, due to a bias resulting from the selection of severely obstructed subjects.", "A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results.\n Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design.\n Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments.\n Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone.", "Inhaled long-acting beta2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone.\n 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 microg salmeterol twice daily (n=372), 500 microg fluticasone twice daily (n=374), 50 microg salmeterol and 500 microg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6h and from study medication for at least 12h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol.\n All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105-161, p<0.0001), salmeterol (73 mL, 46-101, p<0.0001), or fluticasone alone (95 mL, 67-122, p<0.0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration.\n Because inhaled long-acting beta2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD." ]

[ "9534826", "11157431", "10353452", "11989986", "12027240", "9545998", "7953039", "17335327", "16675365" ]

[ "Intensive case management for the severely mentally ill. Controlled trial.", "Intellectual functioning and outcome of patients with severe psychotic illness randomised to intensive case management. Report from the UK700 trial.", "Intensive case management in Australia: a randomized controlled trial.", "Heavy users of acute psychiatric beds: randomized controlled trial of enhanced community management in an outer London borough.", "Outcome of case management based on the strengths model compared to standard care. A randomised controlled trial.", "Randomized trial of general hospital and residential alternative care for patients with severe and persistent mental illness.", "Family-based intervention for schizophrenic patients in China. A randomised controlled trial.", "Are day hospitals effective for acutely ill psychiatric patients? A European multicenter randomized controlled trial.", "Effectiveness of an intervention to reduce sickness absence in patients with emotional distress or minor mental disorders: a randomized controlled effectiveness trial." ]

[ "The aim was to compare the efficacy of intensive clinical case management (ICM) with standard community care in the management of 'hard to treat' patients with a severe mental illness.\n A randomised controlled trial was carried out in East Lambeth, a deprived area of inner London. Seventy people with psychosis designated as 'hard to treat' by referring teams were included; 35 were randomised to ICM (case load eight patients per worker), and 35 to standard care, which offered follow-up by a community psychiatric nursing service (30 patients per worker). Outcome measures were admissions and hospital bed utilisation; contact with services; symptomatology; social behaviour; social functioning; quality of life; patients' satisfaction with care at 9 and 18 months.\n There were no differences in patients' symptoms, social behaviour or social functioning. Quality of life was significantly improved in patients receiving ICM at 9 months. Satisfaction with care was significantly greater among case-managed patients. All ICM patients remained in contact with services throughout the study, while six control patients were refusing all contact with services at 18 months.\n ICM failed to improve the clinical outcome of 'hard to treat' patients. The service was successful in maintaining contact with patients, was greatly appreciated and had a positive effect on their perceived quality of life.", "Little research has been carried out on the benefits of intensive case management (ICM) for people with borderline IQ and severe mental illness.\n To compare outcome and costs of care of patients with severe psychotic illness with borderline IQ to patients of normal IQ and to assess whether ICM is more beneficial for the former than for the latter.\n The study utilises data from the UK700 multi-centre randomised controlled trial of case management. The main outcome measure was the number of days spent in hospital for psychiatric reasons. Secondary outcomes were costs of care and clinical outcome.\n ICM was significantly more beneficial for borderline-IQ patients than those of normal IQ in terms of reductions in days spent in hospital, hospital admissions, total costs and needs and increased satisfaction.\n ICM appears to be a cost-effective strategy for a subgroup of patients with severe psychosis with cognitive deficits.", "This study compared intensive case management (ICM) with standard clinical case management in a well-resourced community mental health service in Australia. A total of 73 severely disabled clients of an existing clinical service were randomly allocated to either ICM (caseload 10 clients per clinician) or standard case management (caseload up to 30 clients per clinician) and followed up for 12 months. A greater proportion of clients receiving ICM showed improved social functioning, these clients had fewer psychiatric hospital admissions involving police, and were more likely to engage and remain in treatment compared to those who received standard case management. Clients receiving ICM did not show a reduction in hospitalization duration or total number of episodes. It is suggested that future studies of ICM should focus on which aspects of treatment produce positive outcomes, how they can be applied to routine clinical settings, and over what period of time outcomes are sustained.", "Heavy users of psychiatric services, often defined as the population that uses the most beds, consume a large part of the resources used by the whole service, despite being relatively small in number. Any intervention that reduces heavy use is therefore likely to lead to significant savings, and enhancement of standard care using a form of intensive case management akin to assertive community treatment was thought to be a pragmatic strategy for testing in this group.\n The effectiveness of enhanced community management (ECM) was compared with standard care alone in heavy users, who represented the 10% of patients with the highest number of hospital admissions and occupied bed days over the previous 6.5 years in an outer London borough. One hundred and ninety-three patients were randomly assigned to ECM or standard care and their use of services was determined after 1 and 2 years, with assessments of costs, clinical symptoms, needs, and social function made before entry into the study and after 1 and 2 years.\n Despite a 24 fold increase in community contacts in the study group, there were no significant differences between the two groups in any of the main outcome measures. Small savings on in-patient and day-hospital service costs were counterbalanced by the increased costs of outpatient and community care for the subjects assigned to ECM. Clinical outcome data derived from interviews in two-thirds of the subjects were similar in both groups.\n Providing additional intensive community focused care to a group of heavy users of psychiatric in-patient services in an outer London borough does not lead to any important clinical gains or reduced costs of psychiatric care.", "The outcome of less intensive case management services, such as the strengths model, is still inconclusive, which suggests a need for more controlled studies. The aim of the present study was to investigate the outcome of a strengths model of case management service (SCM) compared to standard care.\n Seventy-seven clients with a mental illness and a serious impairment in functioning in social contacts, housing or work situation were randomly allocated to SCM or standard care. Outcome was assessed with regard to use of psychiatric services, changes in symptomatology, psychosocial functioning, social network, needs for care, quality of life and client satisfaction with care. The follow-up period was 36 months.\n The results showed a greater reduction in needs for care in clients receiving SCM. No differences in clinical or social outcome were shown. Clients receiving SCM also used significantly less days in psychiatric inpatient services and were generally more satisfied with the psychiatric services offered.\n SCM failed to improve clinical and social outcome compared to standard care, but was more successful in reducing days spent in hospital, and the clients were also more satisfied with the service compared to standard care.", "Severe and persistent mental illnesses are often lifelong and characterized by intermittent exacerbations requiring hospitalization. Providing needed care within budgetary constraints to this largely publicly subsidized population requires technologies that reduce costly inpatient episodes. The authors report a prospective randomized trial to test the clinical effectiveness of a model of acute residential alternative treatment for patients with persistent mental illness requiring hospital-level care.\n Patients enrolled in the Montgomery County, Md., public mental health system who experienced an illness exacerbation and were willing to accept voluntary treatment were randomly assigned to the acute psychiatric ward of a general hospital or a community residential alternative. There were no psychopathology-based exclusion criteria. Treatment episode symptom improvement, satisfaction, discharge status, and 6-month pre- and postepisode acute care utilization, psychosocial functioning, and patient satisfaction were assessed.\n Of 185 patients, 119 (64%) were successfully placed at their assigned treatment site. Case mix data indicated that patients treated in the hospital (N = 50) and the alternative (N = 69) were comparably ill. Treatment episode symptom reduction and patient satisfaction were comparable for the two settings. Nine (13%) of 69 patients randomly assigned to the alternative required transfer to a hospital unit; two (4%) of 50 patients randomly assigned to the hospital could not be stabilized and required transfer to another facility. Psychosocial functioning, satisfaction, and acute care use in the 6 months following admission were comparable for patients treated in the two settings and did not differ significantly from functioning before the acute episode.\n Hospitalization is a frequent and high-cost consequence of severe mental illness. For patients who do not require intensive general medical intervention and are willing to accept voluntary treatment, the alternative program model studied provides outcomes comparable to those of hospital care.", "We developed and evaluated a comprehensive, ongoing intervention for families of schizophrenic patients appropriate for China's complex family relationships and unique social environment.\n Sixty-three DSM-III-R schizophrenic patients living with family members were enrolled when admitted to hospital and randomly assigned to receive standard care or a family-based intervention that included monthly 45-minute counselling sessions focused on the management of social and occupational problems, medication management, family education, family group meetings, and crisis intervention.\n At 6, 12, and 18-month follow-ups by blind evaluators, the proportion of subjects rehospitalised was lower, the duration of rehospitalisation was shorter, and the duration of employment was longer in the experimental group than in the control group; these differences were statistically significant at the 12 and 18-month follow-ups and were not explained by differences in drug compliance. Family intervention was associated with significantly lower levels of family burden.\n This intervention is less costly than standard treatment, is suitable for urban families of schizophrenic patients in China and feasible given the constraints of the Chinese mental health system.", "Acute psychiatric day care has been proposed as an alternative to conventional inpatient care, yet the evidence of its effectiveness is inconsistent and based only on single-site studies in 3 countries. The aim of this multicenter randomized controlled trial was to establish the effectiveness of acute day hospital care in a large sample across a range of mental health care systems.\n The trial was conducted from December 2000 to September 2003 in 5 European countries, with a sample of 1117 voluntarily admitted patients. Immediately before or very shortly after admission to the participating psychiatric facilities, patients were randomly allocated to treatment in a day hospital or an inpatient ward. Psychopathology, treatment satisfaction, subjective quality of life, and social disabilities were assessed at admission, at discharge, and 3 and 12 months after discharge. An intention-to-treat analysis was conducted using fixed-effects linear models with structured error covariance matrices and covariates.\n Day hospital care was as effective as conventional inpatient care with respect to psychopathologic symptoms, treatment satisfaction, and quality of life. It was more effective on social functioning at discharge and at the 3- and 12-month follow-up assessments.\n This study, which has more than doubled the existing evidence base, has shown that day hospital care is as effective on clinical outcomes as conventional inpatient care and more effective on social outcomes.\n ClinicalTrials.gov identifier NCT00153959.", "The purpose of this study was to evaluate the effectiveness of an activating intervention designed to reduce sick leave duration in patients with emotional distress or minor mental disorders.\n In a 1.5-year randomized controlled trial, 194 patients with minor mental disorders received either an experimental intervention by social workers or general practitioners' usual care. The intervention focused on understanding causes, developing and implementing problem-solving strategies and promoting early work resumption. Outcome measures were sick leave duration, mental health and physical health (questionnaires included the Hospital Anxiety and Depression Scale, the Four-Dimensional Symptom Questionnaire and SF-36), all measured at baseline at and 3, 6 and 18 months later. Multilevel analyses were used to evaluate differences between groups.\n The groups did not differ significantly on any of the outcome measures, except that the experimental group reported higher satisfaction with treatment.\n Although the intervention has benefits, it was not successful at its primary goal (i.e., to reduce sick leave duration in patients with emotional distress or minor mental disorders). Programs aimed at the reduction of sick leave duration may yield better results if targeted at patients with more severe emotional problems than at those with exclusively emotional distress or minor mental disorders, or if delivered by caregivers who are closer to the work environment than are social workers, such as occupational physicians." ]

[ "20598077", "19121589", "11288011", "1962900", "10436448", "15457363", "17208082", "10717252", "1962901" ]

[ "PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma.", "A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis.", "Prevention of venous thromboembolism after knee arthroscopy with low-molecular weight heparin (reviparin): Results of a randomized controlled trial.", "Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin.", "Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis.", "Venous thromboembolism prophylaxis after head and spinal trauma: intermittent pneumatic compression devices versus low molecular weight heparin.", "Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms.", "Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial.", "A double-blind and randomized placebo-controlled trial of low molecular weight heparin once daily to prevent deep-vein thrombosis in acute ischemic stroke." ]

[ "Venous thromboembolism (VTE) occurs in 20-30% of patients with malignant glioma per year of survival. We tested the efficacy of long-term dalteparin low-molecular-weight heparin (LMWH) for prevention of VTE in these patients.\n Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti-Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment.\n The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety-nine patients were randomized to LMWH and 87 to placebo. Twenty-two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19-1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48-36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12-month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73-2.0, P = 0.48).\n Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long-term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.\n © 2010 International Society on Thrombosis and Haemostasis.", "To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT).\n A randomised, open-label trial.\n In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months.\n During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group.\n Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer.", "Deep venous thrombosis (DVT) is a common, important complication of major orthopaedic surgery, particularly knee arthroplasty. Knee arthroscopy is increasingly performed on an outpatient basis. Few reports have elucidated the incidence of venous thromboembolism (VTE) in patients undergoing arthroscopic surgery receiving no prophylaxis. The objective of the present trial was to evaluate the risk of VTE in those patients and to determine efficacy and safety of a low-molecular weight heparin (LMWH) in preventing VTE.\n This is the first controlled randomized trial using objective diagnostic methods with blinded outcome assessment to reveal the incidence of VTE in outpatient arthroscopy and determine efficacy and safety of a LMWH (reviparin sodium) in preventing VTE in these patients.\n There were 262 patients undergoing elective knee arthroscopy prospectively randomized to receive either no treatment or reviparin once daily subcutaneously for 7 to 10 days. The blindly assessed primary outcome measure was the incidence of DVT detected by compression color-coded sonography. Both groups were comparable with regard to demographics and baseline characteristics.\n 239 patients were evaluable (122 no treatment, 117 receiving LMWH). 6 DVT were detected - 5 in the control group (5/117 - 4.1%) and only one in the active treatment group (1/116 - 0.85%). This particular patient had a low level of protein C and a subnormal level of protein S. The odds ratio of 4.95 approximates a relative risk reduction of about 80%. Treatment with reviparin was safe and well tolerated. There was no major bleeding, four patients with minor bleedings. One patient had a transitory fall in platelet count below 100 giga-particles/L without any clinical symptoms.\n Patients undergoing knee arthroscopy have a moderate risk of VTE and effective prophylaxis can be achieved with LMWH (reviparin).", "A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a LMWH fragment (Kabi 2165, Fragmin) for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the fragment was given in the evening before surgery, and thereafter every evening. There were 1002 analyzable patients, 826 having received correct prophylaxis. Sixty three percent of the patients were operated on for malignant diseases. The frequency of DVT was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2 to 5.0%, p = 0.02). In patients with malignancies the reduction was from 11.2 to 6.4% (p = 0.06). The frequency of bleeding was 6.7% among the heparin fragment patients and 2.7% among the patients given conventional heparin (p = 0.01). The corresponding frequencies for patients with malignancies were 3.2 and 2.8%, respectively (p = 0.28). All bleedings were minor and of no clinical significance. Local pain at the injection site was reported significantly less often among patients with the fragment. Twenty patients died, 13 with malignant disease, mortality being the same in the two groups. It is concluded that heparin fragment administered in the evening before surgery and then every evening is a practically acceptable alternative to prevent postoperative DVT in patients undergoing elective abdominal surgery, also when the histology shows malignancy. Thus, the advantages of using LMWH compared with conventional low-dose heparin are simplified administration routines, better thromboprophylactic effect, and less local pain at injection sites. A disadvantage is the slight increase in hemorrhagic side effects, all of minor clinical importance and not seen in patients undergoing surgery for malignancy.", "The primary objective of this study was to evaluate with venography the rate of thrombus regression after a fixed dose of low-molecular weight heparin (LMWH) per day for 3 months compared with oral anticoagulant therapy for deep venous thrombosis (DVT). Secondary endpoints were the comparisons of the efficacy and safety of both treatments.\n This study was designed as an open randomized clinical study in a university hospital setting. Of the 165 patients finally enrolled in the study, 85 were assigned LMWH therapy and 80 were assigned oral anticoagulant therapy. In the group randomized to oral anticoagulant therapy, the patients first underwent treatment in the hospital with standard unfractionated heparin and then coumarin for 3 months. Doses were adjusted with laboratory monitoring to maintain the international normalized ratio between 2.0 and 3.0. Patients in the LMWH group were administered subcutaneous injections of fixed doses of 40 mg enoxaparin (4000 anti-Xa units) every 12 hours for 7 days, and after discharge from the hospital, they were administered 40 mg enoxaparin once daily at fixed doses for 3 months without a laboratory control assay. A quantitative venographic score (Marder score) was used to assess the extent of the venous thrombosis, with 0 points indicating no DVT and 40 points indicating total occlusion of all deep veins. The rate of thrombus reduction was defined as the difference in quantitative venographic scores after termination of LMWH or coumarin therapy as compared with the scores obtained on the initial venographic results. The efficacy was defined as the ability to prevent symptomatic extension or recurrence of venous thromboembolism (documented with venograms or serial lung scans). The safety was defined as the occurrence of hemorrhages.\n After 3 months of treatment, the mean Marder score was significantly decreased in both groups in comparison with the baseline score, although the effect of therapy was significantly better after LMWH therapy (49.4% reduction) than after coumarin therapy (24.5% reduction; P <.001). LMWH therapy and male gender were independently associated with an enhanced resolution of the thrombus. A lower frequency of symptomatic recurrent venous thromboembolism was also shown in patients who underwent treatment with LMWH therapy (9.5%) than with oral anticoagulant therapy (23.7%; P <.05), although this difference was entirely a result of recurrence of DVT. Bleeding complications were significantly fewer in the LMWH group than in the coumarin group (1. 1% vs 10%; P <.05). This difference was caused by minor hemorrhages. Coumarin therapy and cancer were independently associated with an enhanced risk of complications. Subcutaneous heparin therapy was well tolerated by all patients.\n The patients who were allocated to undergo enoxaparin therapy had a significantly greater improvement in their quantitative venographic score, a significantly lower recurrence rate of symptomatic venous thromboembolism, and a significantly lower incidence of bleeding than patients who underwent treatment with coumarin. LMWH can be used on an outpatient basis as a safer and more effective alternative to classical oral anticoagulant therapy for the secondary prophylaxis of selected patients with DVT.", "Although there are alternative methods and drugs for preventing venous thromboembolism (VTE), it is not clear which modality is most suitable and efficacious for patients with severe (stable or unstable) head/spinal injures. The aim of this study was to compare intermittent pneumatic compression devices (IPC) with low-molecular-weight heparin (LMWH) for preventing VTE. We prospectively randomized 120 head/spinal traumatized patients for comparison of IPC with LMWH as a prophylaxis modality against VTE. Venous duplex color-flow Doppler sonography of the lower extremities was performed each week of hospitalization and 1 week after discharge. When there was a suspicion of pulmonary embolism (PE), patients were evaluated with spiral computed tomography. Patients were analyzed for demographic features, injury severity scores, associated injuries, type of head/spinal trauma, complications, transfusion, and incidence of deep venous thrombosis (DVT) and PE. Two patients (3.33%) from the IPC group and 4 patients (6.66%) from the LMWH group died, with their deaths due to PE. Nine other patients also succumbed, unrelated to PE. DVT developed in 4 patients (6.66%) in the IPC group and in 3 patients (5%) in the LMWH group. There was no statistically significant difference regarding a reduction in DVT, PE, or mortality between groups ( p = 0.04, p > 0.05, p > 0.05, respectively). IPC can be used safely for prophylaxis of VTE in head/spinal trauma patients.", "A substantial clinical need exists for an alternate to vitamin K antagonists for treating deep vein thrombosis in many patients. Long-term low-molecular-weight heparin (LMWH), body-weight adjusted, avoids anticoagulant monitoring and may be associated with less bleeding. We evaluated the effectiveness and safety of long-term LMWH compared with vitamin K antagonist therapy in a broad spectrum of patients with proximal vein thrombosis.\n We performed a multicenter, randomized, open-label clinical trial using objective outcome measures comparing therapy for 3 months. Outcomes were assessed at 3 and 12 months.\n Of 737 patients, 18 of 369 receiving tinzaparin (4.9%) had recurrent venous thromboembolism at 3 months compared with 21 of 368 (5.7%) receiving usual care (absolute difference, -0.8%, 95% confidence interval -4.1-2.4). Hemorrhagic complications occurred less frequently in the LMWH group largely because of less minor bleeding: 48 of 369 patients (13.0%) versus 73 of 368 patients (19.8%) receiving usual-care anticoagulation (absolute difference -6.8%; P = .011; risk ratio = 0.66). New major bleeding events ceased early (by day 23, P = .034) for patients receiving LMWH but persisted throughout the study treatment interval for patients receiving vitamin K antagonist therapy. No mortality advantage was shown for LMWH.\n Our study shows that LMWH is similar in effectiveness to the usual-care vitamin K antagonist treatment for preventing recurrent venous thromboembolism in a broad spectrum of patients. It causes less harm and enhances the clinicians' therapeutic options for patients with proximal deep vein thrombosis. Our findings reported here suggest the possibility of a broader role for long-term LMWH in selected patients.", "Recent studies suggest that low molecular weight heparin (LMW heparin) therapy in malignancy may improve cancer survival following surgical resection. We studied prospectively whether cancer mortality during follow-up in women with previously untreated breast, and pelvic cancer is reduced in those who randomly received LMW heparin (Certoparin) compared to patients given unfractionated heparin (UF heparin) for thrombosis prophylaxis during primary surgery. In a prospective, randomized, double-blind clinical trial, 160 patients received Certoparin and 164 UF heparin until post-operatively day 7. Survival estimations are based on the outcome data from a subset of 140 LMW heparin - and 147 UF heparin recipients. Long-term survival in the Certoparin group compared to the UF heparin group was significantly improved after 650 days (P=0. 0066) but not thereafter when analysis was performed on all cancer cell types combined. In the probability estimates survival benefit within this time was restricted to patients with pelvic cancer but was not observed in breast cancer. However, in breast cancer patients who received LMW heparin the impact of classical tumor prognostic markers was statistically significant after 1,050 days but not after 650 days. Thus, breast cancer patients with unfavorable prognosis seem to benefit in terms of survival advantage from LMW heparin within the 650 days after surgery. These results suggest that improvement in cancer survival can be achieved after even a short course of treatment with LMWH (compared to UFH) given for DVT prophylaxis in the post-operative period. An effect of UFH on disease outcome is not excluded. Further definitive trials of LMWH vs. placebo for cancer outcome (rather then DVT) using doses and schedules that may be more optimal are indicated.", "The effect of LMW heparin (Kabi 2165, Fragmin) was compared with placebo for the prevention of DVT in 103 patients with acute ischemic stroke using a prospective, double-blind, randomized trial design. Treatment was started within 72 hours, and LMW heparin was administered subcutaneously once daily according to body weight classes, which corresponded to about 55 to 65 Factor-Xa inhibitory U/kg, for 14 days, or until discharge from the hospital, if earlier. All patients underwent thrombosis surveillance with unilateral venography of the paretic limb. Evaluation of venography could be performed in 42 of 52 patients randomized to LMW heparin and in 50 of 51 patients randomized to placebo. The frequency of DVT was 15 of 42 patients or 36% (95% confidence interval 22 to 52%) in the LMW heparin group and 17 of 50 patients or 34% (21 to 49%) in the placebo group. The frequency of proximal thrombi was 5 of 42 (12%) and 8 of 50 (16%), respectively. There was one fatal pulmonary embolism in the placebo group. The mortality rate (28 days follow-up) was 5 of 52 in the LMW heparin group and 1 of 51 in the placebo group (p = 0.24). None of the deaths was related to treatment. No major hemorrhagic complications were observed. The mean Factor Xa inhibitory activity levels at peak concentration were 0.34 U/ml on day 2 and 0.42 U/ml on day 12 (p = 0.02). We conclude that LMW heparin in the dose range studied did not provide efficient prophylaxis against DVT in patients with acute ischemic stroke." ]

[ "15179608", "20145608", "22472744", "2494098", "17604300", "16572062", "7939431", "15740542", "18469732" ]

[ "Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea.", "Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients.", "Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.", "Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study.", "Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial.", "Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a prospective study.", "Treatment of Clostridium difficile associated diarrhea and colitis with an oral preparation of teicoplanin; a dose finding study. The Swedish CDAD Study Group.", "Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial.", "Probiotic Escherichia coli Nissle 1917 versus placebo for treating diarrhea of greater than 4 days duration in infants and toddlers." ]

[ "Colonic infection with Clostridium difficile, leading to pseudomembranous colitis, is a common complication of antibiotic therapy, especially in elderly patients. It has been suggested that non-pathogenic probiotic bacteria might prevent the development and recurrence of C. difficile infection. This double-blind, placebo-controlled study examines the role of probiotic administration in the prevention of C. difficile-associated diarrhoea (CDAD) in elderly patients receiving antibiotic therapy. Consecutive patients (150) receiving antibiotic therapy were randomised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or placebo for 20 days. Upon admission to hospital, bowel habit was recorded and a faecal sample taken. Trial probiotic or placebo was taken within 72 h of prescription of antibiotics, and a second stool sample was taken in the event of development of diarrhoea during hospitalisation or after discharge. Of the randomised patients, 138 completed the study, 69 with probiotics in conjunction with antibiotics and 69 with antibiotics alone. On the basis of development of diarrhoea, the incidence of samples positive for C. difficile-associated toxins was 2.9% in the probiotic group compared with 7.25% in the placebo-control group. When samples from all patients were tested (rather than just those developing diarrhoea) 46% of probiotic patients were toxin-positive compared with 78% of the placebo group.", "Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.\n In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days.\n Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1.\n The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).", "Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients.\n A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment.\n Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60).\n In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.", "Saccharomyces boulardii, a nonpathogenic yeast, has been widely used in Europe to prevent antibiotic-associated diarrhea (AAD). We performed a prospective double-blind controlled study to investigate AAD in hospitalized patients and to evaluate the effect of S. boulardii, a living yeast, given in capsule form concurrently with antibiotics. Over 23 mo, 180 patients completed the study. Of the patients receiving placebo, 22% experienced diarrhea compared with 9.5% of patients receiving S. boulardii (p = 0.038). Risk factors found to be associated with AAD were multiple antibiotic combinations (containing clindamycin, cephalosporins, or trimethoprim-sulfamethoxazole) and tube feeding. Clostridium difficile, an anaerobe found in the stools of most patients with pseudomembranous colitis, was variably associated with AAD. We evaluated the role of C. difficile in AAD in the study population and found no significant association between the presence of C. difficile or cytotoxin with AAD. Approximately 33% of the patients without diarrhea harbored at least one C. difficile-positive stool and nearly 50% of these patients had detectable cytotoxin. Similar values were obtained in patients with diarrhea. Of C. difficile-positive patients, 31% (5/16) on placebo developed diarrhea compared with 9.4% (3/32) on S. boulardii; this difference was not statistically significant (p = 0.07). There were no discernable adverse effects of yeast administration. We conclude that S. boulardii reduces the incidence of antibiotic-associated diarrhea in hospitalized patients.", "To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile.\n Randomised double blind placebo controlled study.\n 135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis.\n Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake.\n Primary outcome: occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea.\n 7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14).\n Consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50.\n National Research Register N0016106821.", "Interest to probiotics for the prevention and treatment of antibiotic-associated diarrhea is increasing gradually. The most promising seems to be Saccharomyces boulardii . Using a double-blind controlled study, we investigated the preventive effect of S. boulardii on the development of antibiotic-associated diarrhea in patients under antibiotherapy but not requiring intensive care therapy.\n All the patients were hospitalized at the Gulhane Military Medical Academy, Department of Infectious Diseases and Clinical Microbiology. S. boulardii was given twice daily during the course of antibiotic therapy and application was initiated in all patients as late as after 48 hours of antibiotic therapy. A total of 151 patients completed the study.\n The antibiotic-associated diarrhea development ratio in placebo group was 9% (7/78) and in the study group 1.4% (1/73) (p < 0.05). Stool samples from the patients with antibiotic-associated diarrhea were stored at -70 degrees C and Clostiridium difficile toxin A assay was performed using Enzyme Immune Assay as late as in seven days. C. difficile toxin A assay yielded positive results in two (2/7) stool samples from the patients with antibiotic-associated diarrhea in the placebo group and a negative result in the only patient who developed antibiotic-associated diarrhea in the study group.\n The results implied that prophylactic use of Saccharomyces boulardii resulted in reduced, with no serious side effects, antibiotic-associated diarrhea in hospitalized patients.", "92 patients with antibiotic-associated diarrhea were randomized to receive oral teicoplanin 100 mg twice daily for 7 days (BID group); or 50 mg 4 times daily for 3 days, followed by 100 mg twice daily for 4 days (QID group) in a randomized, double-blind, multicentre study. Clostridium difficile was demonstrated by culture and/or cytotoxin test in 49 (53%) patients, of whom 47 (23 male, 24 females, mean age 65 years; 23 in the BID group, 24 in the QID group) were evaluable for clinical efficacy. Prior treatment with cephalosporins was registered in 49%, isoxazolyl-penicillins in 33% and clindamycin in 20% of the C. difficile positive patients. On the last day of treatment, 96% (23 of 24 patients) in the QID group were found cured, compared with 70% (16 of 23 patients) in the BID group (p = 0.02). On days 2 and 3 of treatment, QID group patients had significantly fewer loose stools per day (p < 0.05) than those of the BID group. Clinical recurrence, within 4 weeks post-treatment, occurred in 35% and 33% of the patients in the BID and QID groups, respectively. The bacteriological elimination rate 4 weeks post-treatment was 55% in the BID group and 59% in the QID group. The study was terminated prematurely due to the unexpectedly high clinical failure and recurrence rate in C. difficile positive patients treated with the BID dosage regimen.", "Co-treatment with Saccharomyces boulardii appears to lower the risk of antibiotic-associated diarrhoea in adults receiving broad-spectrum antibiotics.\n To determine whether S. boulardii prevents antibiotic-associated diarrhoea in children.\n A total of 269 children (aged 6 months to 14 years) with otitis media and/or respiratory tract infections were enrolled in a double-blind, randomized placebo-controlled trial in which they received standard antibiotic treatment plus 250 mg of S. boulardii (experimental group, n = 132) or a placebo (control group, n = 137) orally twice daily for the duration of antibiotic treatment. Analyses were based on allocated treatment and included data from 246 children.\n Patients receiving S. boulardii had a lower prevalence of diarrhoea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) than those receiving placebo [nine of 119 (8%) vs. 29 of 127 (23%), relative risk: 0.3, 95% confidence interval: 0.2-0.7]. S. boulardii also reduced the risk of antibiotic-associated diarrhoea (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared with placebo [four of 119 (3.4%) vs. 22 of 127 (17.3%), relative risk: 0.2; 95% confidence interval: 0.07-0.5]. No adverse events were observed.\n This is the first randomized-controlled trial evidence that S. boulardii effectively reduces the risk of antibiotic-associated diarrhoea in children.", "Administering probiotics can prevent or cure some forms of diarrhea. The efficacy of probiotic Escherichia coli Nissle 1917 (EcN) in infants and toddlers with diarrhea >4 days was tested by a double-blind trial.\n One hundred fifty-one children aged 1-47 months with nonspecific diarrhea were randomized to receive either EcN suspension (N = 75) or placebo (N = 76). Diarrhea had to meet the following definition: >3 watery or loose nonbloody stools in 24 hours of a diarrheal episode persisting for >4 consecutive days but < or =14 days. All children were well nourished or only moderately malnourished, mildly dehydrated, and received oral rehydration at study commencement. They were treated orally with 1-3 mL EcN suspension (1 mL contains 10 viable cells) or placebo daily for 21 days. Primary objective was to confirm a better response rate (reduction of daily stool frequency to < or =3 watery or loose stools over > or =4 days) with EcN.\n The 7-day response was higher for the EcN group than placebo (EcN 78.7%, placebo 59.2%). Significant differences were observed on days 14 (EcN 93.3%, placebo 65.8%, P = 0.0017) and 21 (EcN 98.7%, placebo 71.1%, P < 0.001). Kaplan-Meier survival analysis resulted in a significant difference of 3.3 days between the groups (P < 0.0001); median time to response for EcN was 2.4 and 5.7 for placebo. EcN was safe and well tolerated.\n In the conditions of this trial EcN was a suitable remedy for diarrhea >4 days in young children." ]

[ "33086", "8330429", "16675091", "12380631", "3908675", "2866117", "6133791", "7028529", "2179780" ]

[ "Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium.", "An attempt at real prophylaxis of primary dysmenorrhea: comparison between meclofenamate sodium and naproxen sodium.", "The efficacy and safety of aceclofenac versus placebo and naproxen in women with primary dysmenorrhoea.", "Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies.", "Efficacy of fenoprofen in the treatment of primary dysmenorrhea.", "Ibuprofen and naproxen-sodium in the treatment of primary dysmenorrhea: a double-blind cross-over study.", "Dysmenorrhea in women with intrauterine contraceptive device. Treatment with a prostaglandin synthetase inhibitor, naproxen.", "Treatment of primary dysmenorrhea with diclofenac sodium.", "Transcutaneous electrical nerve stimulation (TENS) for the treatment of primary dysmenorrhea: a randomized crossover comparison with placebo TENS and ibuprofen." ]

[ "Thirty-two dysmenorrheic patients participated in a double-blind trial of naproxen sodium for three consecutive menstrual cycles. The women were divided into two groups: 15 women were given naproxen sodium (the sodium salt of d-2-(6-methoxy-2-naphthyl) propionic acid) and 17 women received placebo tablets. The women were prescribed two tablets (550 mg) at the first sign of menstrual pain and one tablet (275 mg) thereafter every six hours, as required. There were no significant differences between the two groups in physical characteristics, obstetric and gynecologic histories, including the character of dysmenorrhea and pretreatment pain intensity scores (p = 0.7). Following intake of the drug or placebo, the participants rated the relief provided by the medication with a six-point scoring system. When the scores for pain relief were tallied for the three treatment cycles, the naproxen sodium group averaged 13.7 +/- 0.65 standard error, while the placebo group averaged 8.8 +/- 0.95 standard error out of a possible maximum relief score of 18. The difference between the two groups was statistically significant at p = 0.0004. Few patients reported side effects.", "Dysmenorrhea is a widespread phenomenon, affecting mainly young nulliparous women, often inducing difficulties in study or in work. Its pathogenesis involves a release of local vasoconstrictors like Prostaglandins and Leukotrienes. Modern therapy is based firstly on the administration of prostaglandin-Synthetase Inhibitors or Contraceptive Pills, with the aim of reducing the menstrual excess of pain inducing substances. In order to achieve more efficacy, on the basis of the already proven effectiveness of the Non Steroid Anti-Inflammatory Drugs (NSAID)s in this field, we recently set out to prevent dysmenorrhea in a double-blind randomized study with Meclofenamate Sorium and Naproxen Sodium. Through the observation of the drop in Basal Body Temperature which usually precedes menstrual flow, we were able to instruct our patients in the earlier recognition of impending menstrual onset, leading to earlier prevention of Prostaglandin and Leukotriene release. Meclofenamate Sodium in particular led to considerable pain reduction, with very good patient compliance and without significant complications, probably of its additional receptor effect.", "To determine the analgesic efficacy and safety of a single oral dose of aceclofenac 100 mg and compare that with placebo and naproxen 500 mg in women with primary dysmenorrhoea.\n In this double-blind, prospective, multicentre, randomised, three-way, crossover study, women were randomly assigned to receive one of six treatment sequences, comprising single oral doses of aceclofenac 100 mg, naproxen 500 mg or placebo, when menstrual pain reached a predetermined level of severity. A single dose of the assigned study medication was taken on three menstrual periods; a different medication was taken on each treatment day. Analgesic efficacy was determined by self-reported analgesia scoring and participants' and investigators' global evaluation of treatment effectiveness. Measurements also included physical examination and adverse events.\n Total pain relief scores were not statistically significantly different for aceclofenac and naproxen, and both were statistically significantly more effective than placebo (p = 0.019 and 0.002, respectively). This finding was supported by secondary endpoints including sum of pain intensity differences (SPID/8), peak analgesia (peak pain intensity and peak pain relief), and participants' and investigators' overall evaluation of effectiveness. Both aceclofenac and naproxen were well tolerated.\n Aceclofenac (100 mg) and naproxen (500 mg) effectively treated the pain associated with primary dysmenorrhoea, and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria.", "Dysmenorrhea is the most common menstrual complaint in young women, with a prevalence as high as 90%. It is responsible for substantial repeated short-term absenteeism from school and work in young women. Effective treatments are available, including nonsteroidal anti-inflammatory drugs (NSAIDs). In many countries, a variety of NSAIDs have become available as over-the-counter (OTC) drugs.\n The goal of this study was to compare the efficacy and safety of OTC doses of naproxen (400 mg) and naproxen/naproxen sodium (200/220 mg) with acetaminophen (1000 mg), ibuprofen (200 mg), and placebo in the treatment of primary dysmenorrhea.\n A pooled analysis of 5 trials was performed. Efficacy was assessed by pain relief, relief of other dysmenorrheic symptoms, time to backup medication or remedication, and treatment preference. Tolerability was assessed by recording adverse events (AEs).\n A total of 443 women were enrolled in the combined studies. Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration (P < 0.01 and P < 0.05, respectively). Furthermore, naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen (P < 0.01 and P < 0.05, respectively) and ibuprofen (P < 0.001 and P < 0.01, respectively) at 6 hours after administration. Both doses of naproxen had higher scores than placebo for symptom relief and drug preference (all P < 0.001). The AEs and their frequency were similar among the treatment groups. No serious AEs were reported.\n When administered at OTC doses, naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied.", "We compared fenoprofen calcium, 200 mg; fenoprofen calcium, 400 mg; aspirin, 650 mg; and a placebo in 85 women for the relief of primary dysmenorrhea in a double-blind, clinical trial. The usefulness of these drugs was judged from data obtained over four consecutive menstrual periods on: restriction of daily activity, pain intensity scores, need for rescue analgesics, withdrawal due to lack of efficacy, and adverse events. Both fenoprofen, 200 mg, and fenoprofen, 400 mg, offered significant (P less than .01) pain relief when compared to placebo and aspirin. Analyses of data on 1, 2 and 3 indicated that aspirin was not significantly different from placebo. The aspirin-treated group reported the greatest number of adverse reactions, but the differences between the four groups were not statistically significant. Our study lends support to the concept of a \"plateau analgesic effect\" of nonsteroidal antiinflammatory drugs (NSAIDs): fenoprofen, 200 mg, appears to be as effective as fenoprofen, 400 mg. When this type of drug fails to provide relief for a woman suffering from primary dysmenorrhea, switching to another NSAID may be more appropriate than increasing the dosage and the probability of dosage-related side effects.", "The efficacy of ibuprofen and naproxen-sodium for the treatment of primary dysmenorrhea was evaluated in a double-blind cross-over study in 57 otherwise healthy women. The severity of pain reported by the patients was significantly (P less than 0.01) reduced during treatment with both ibuprofen and naproxen-sodium compared to the severity of pain before the first dose. The mean pain relief during treatment with ibuprofen was significantly (P less than 0.05) greater than during treatment with naproxen-sodium in the dosages indicated.", "Twenty-one women with intrauterine contraceptive devices (IUCD) and severe dysmenorrhea were studied. All the women who participated in the study had primary dysmenorrhea of varying intensities. The insertion of IUCD increased the intensity of dysmenorrheic pain. The effect of naproxen (Naprosyn) on pain alleviation was studied in a double-blind cross-over trial using naproxen and placebo. The effect of naproxen was significantly better than that of placebo (P less than 0.01). No severe side effects occurred during the treatment. There was no difference in the duration and amount of the menstrual blood flow during naproxen treatment compared to placebo according to the women's own judgement.", "The efficacy of diclofenac sodium was investigated in the painful symptoms of primary dysmenorrhea and in reducing menstrual bleeding. Thirty-five nulliparous women (17-28 yr of age) were included in a double-blind cross-over study for four menstrual periods, two periods with diclofenac sodium and two periods with placebo. The diclofenac sodium treatment (total of 58 periods) reduced the pain significantly in comparison with placebo (57 periods), as evaluated by subjective rating (P less than 0.001) and by a 6-point scale of pain intensity (P less than 0.05). Also the amount of menstrual bleeding was significantly reduced as measured by subjective rating (P less than 0.001) and by counting the number of sanitary pads used (P less than 0.05). The results indicate that diclofenac sodium in low dose (about 75 mg daily) is effective not only in reducing the pain at menstruation, but also the bleeding.", "In a randomized four-way crossover study, 32 women with primary dysmenorrhea were treated with transcutaneous electrical nerve stimulation (TENS) for two cycles, placebo (sham) TENS for one cycle, or ibuprofen 400 mg four times a day for one cycle. The TENS setting used was 100 pulses per second with 100-microsecond pulse widths. The subjects were allowed to adjust the amplitude to a comfortable level. The pain rescue medication was ibuprofen 400 mg as needed, up to 1600 mg/day. Significantly more subjects who had TENS treatment did not require rescue medication or required less backup ibuprofen at 0-4, 4-8, and 8-12 hours after the onset of dysmenorrhea and starting treatment, as well as during the first 24 hours and for the duration of the menstrual flow, when compared with placebo TENS or ibuprofen-treated cycles (Tukey multiple comparison, P less than .01). Transcutaneous electrical nerve stimulation significantly delayed the need for ibuprofen by an average of 5.9 hours, compared with 0.7 hours when using ibuprofen alone (P less than .05, paired t test). Transcutaneous electrical nerve stimulation alone provided good to excellent subjective pain relief in 42.4% of subjects, compared with 3.2% with placebo TENS, and significantly reduced diarrhea, menstrual flow, clot formation, and fatigue compared with placebo TENS. Transcutaneous electrical nerve stimulation plus less ibuprofen provided pain relief equivalent to that obtained with ibuprofen alone (71 and 75% of the subjects, respectively). We conclude that TENS is a safe, effective, non-medication method for managing primary dysmenorrhea and that TENS plus ibuprofen was the best overall treatment, as indicated by pain relief." ]

[ "16225575", "20005647", "10453830", "2437967", "7947529", "14747165", "16001749", "12625668", "12592250" ]

[ "First trimester threatened miscarriage treatment with human chorionic gonadotrophins: a randomised controlled trial.", "Dydrogesterone in threatened miscarriage: a Malaysian experience.", "Randomised trial comparing expectant with medical management for first trimester miscarriages.", "Double-blind controlled trial of progesterone substitution in threatened abortion.", "Early abortion induction by a combination of mifepristone and oral misoprostol: a comparison between two dose regimens of misoprostol and their effect on blood pressure.", "A randomized controlled trial comparing medical and expectant management of first trimester miscarriage.", "[Comparative study of the effect of intravaginal misoprostol at 50 and 100 micrograms in cervical ripening and labor induction].", "Methyldopa versus no drug treatment in the management of mild pre-eclampsia.", "Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study." ]

[ "To determine whether administration of exogenous human chorionic gonadotrophin (hCG) treatment improve the pregnancy outcome in first trimester threatened miscarriages.\n A prospective, double blind, randomised, placebo-controlled trial.\n The Early Pregnancy Assessment Unit, Royal Bolton Hospital, Bolton, United Kingdom.\n One hundred and eighty-three women with vaginal bleeding and a viable fetus seen on ultrasound scan (USS) in the first 12 weeks of pregnancy.\n The patients were randomised to receive either hCG or placebo treatment until 14 weeks of gestation.\n The primary objective of the trial was to determine the miscarriage rate in the hCG arm compared from the placebo arm.\n Of the 183 cases, 87 were randomised to treatment with hCG while 96 were randomised to receive a placebo. Forty-seven (25%) did not comply with the study protocol. The mean [SD] gestational age at presentation was 7 [1.33] weeks. The mean [SD] age of women in study was 27 [5] years in the placebo and 28 [5] in the hCG group. The mean body mass index (kg/m(2)) was 25 [5] in the study. The number of patients actively bleeding per vaginum at presentation was 85 (93%) in placebo group and 79 (96%) in the hCG group. The median number of hCG or placebo injections for both groups was 7. Ten women (11%) in the placebo group proceeded to have a complete miscarriage, as did 10 women (12%) in the hCG group, relative risk (RR) [95% confidence interval (CI)] of 1.1 (0.63-1.6).\n Our study showed no evidence of a difference in the outcome of threatened miscarriages when treated with hCG in the first trimester, this may be because our study sample size was small and follow up was suboptimal. A large, randomised, multicentre trial is still needed to establish the usefulness of hCG treatment in cases of threatened miscarriage.", "Threatened miscarriage is a common problem during pregnancy.\n The aim of this prospective, open, randomised study was to determine whether dydrogesterone was more effective than conservative management alone in preventing miscarriage in women with vaginal bleeding up to week 16 of pregnancy. Women were excluded if they had a history of recurrent miscarriage. A total of 191 women were randomised to dydrogesterone (40 mg stat followed by 10mg twice daily) or conservative management (control group). The treatment was considered successful if the pregnancy continued beyond 20 weeks of gestation.\n The success rate in the dydrogesterone group was statistically significantly higher than that in the control group (87.5% vs. 71.6%; p<0.05). Miscarriage occurred in 12.5% of women in the dydrogesterone group compared with 28.4% in the control group (p<0.05). There were no differences between the groups with regard to the incidence of Caesarean section, placenta praevia, antepartum haemorrhage, preterm labour (weeks 28-36), pregnancy-induced hypertension or low birth weight (<2500 g) babies. There were no intrauterine deaths or congenital abnormalities in either group.\n Compared with conservative management, dydrogesterone had beneficial effects on maintaining pregnancy in women with threatened miscarriage.\n Copyright 2009 Elsevier Ireland Ltd. All rights reserved.", "To compare the efficacy of antiprogesterone (mifepristone) in combination with a synthetic prostaglandin E1 analogue (misoprostol) for outpatient treatment of miscarriages.\n One hundred and twenty-two women with first trimester miscarriages.\n The women were randomised to treatment with mifepristone 400 mg orally followed by a single oral dose of 400 microg misoprostol 48 hours later (n = 60) or expectant management (n = 62). Women were re-evaluated five days later. If retained intrauterine products of conception were found with an antero-posterior diameter above 15 mm on transvaginal ultrasound, surgical evacuation was performed.\n Eighty-two percent of the women randomised to pharmacological treatment and 76% of those randomised to expectant management had an empty uterine cavity after five days. Convalescence time was 1.8 days longer for women randomised to pharmacological treatment. Pain, bleeding, complications, and satisfaction with the treatment did not differ between the groups.\n Most cases of spontaneous incomplete miscarriage will become a complete miscarriage without intervention. This study shows that outpatient treatment with a combination of antiprogesterone and a prostaglandin E1 analogue did not increase the rate of complete miscarriage, compared with expectancy alone, by a clinical important degree.", "Between 1983 and 1984 a double-blind randomized study with progesterone substitution in threatened abortion was carried out. Fifty-six patients with vaginal bleeding during the first trimester of pregnancy, the internal cervical os being closed, were referred to the hospital. Twenty-five women (5th and 6th week of gestation) with positive serum concentrations of beta-hCG were admitted to the study without regard to sonogram results. In other 25 women (7th-10th week of pregnancy) and 6 women (greater than or equal to 11th week of pregnancy) fetal heart action and movement could be demonstrated by ultrasound. The patients were prescribed bed rest and vaginal suppositories twice daily, containing either 25 mg progesterone or only polyethylene glycol. The code was not broken until after completion of the study. Serial serum determinations of beta-hCG, estradiol-17 beta (E2), progesterone, and ultrasound were performed. Four patients had to be omitted from final analysis (two tubal pregnancies, one intrauterine infection, one sectio parva). Three of 26 patients progesterone (11%) and five of 26 patients with placebo (19%) had an abortion, which represented no significant difference. Frequency of abortion was increased in women more than 30 years old, in women with previous abortions and after ovulation induction. Progesterone treatment resulted in a significant elevation of serum progesterone concentrations (p less than 0.01), while beta-hCG and E2 were unchanged. The results of this study confirm that pregnancy outcome is favorable in women with bleeding and normal hormone concentrations without hormonal treatment and unfavorable in women with reduced beta-hCG and E2-concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)", "1. To investigate the efficacy of 800 micrograms misoprostol (a PGE1 analogue) when administered to women pretreated with mifepristone for early pregnancy termination. 2. To establish means of minimising gastrointestinal side effects by comparing two different misoprostol regimens. The impact of these regimens on blood pressure was investigated in a subgroup of patients.\n A randomised study of 150 women of 56 days gestation, or less, allocated to receive oral misoprostol either in a single dose of 800 micrograms or as two doses of 400 micrograms administered sequentially 2 h apart; in each case misoprostol was administered 36 to 48 h after receiving mifepristone 200 mg orally.\n Complete abortion rates, the frequency and severity (patients' perception) of gastrointestinal side effects, and blood pressure changes in response to prostaglandin administration.\n The overall success rate was 93%. Seventy-one (95%) women who received a single dose of misoprostol and sixty-nine (92%) who received the sequential dose aborted completely. There were two ongoing pregnancies in the first group (2.5%) and three (4%) in the second. The overall ongoing pregnancy rate was 3%. The incidence of diarrhoea was significantly lower for women receiving the sequential dose, and no significant differences were found in the incidence of the other gastrointestinal side effects. The only noted significant change in blood pressure was in diastolic pressure 4 h after the administration of the higher dose of prostaglandin, but this was slight.\n The combination of mifepristone and oral misoprostol provides an alternative method to inducing abortion of pregnancies of up to eight weeks gestation. Patients receiving the single dose of 800 micrograms were more troubled by diarrhoea than those on the sequential regimen. The ongoing pregnancy rate was higher than previously reported with vaginal or parenteral administration of prostaglandin.", "We aimed to determine whether outpatient treatment of miscarriage with vaginal misoprostol is more effective than expectant management in reducing the need for surgical evacuation of retained products of conception (ERPC).\n Of 131 eligible women with first trimester miscarriage, 104 agreed to randomization to either 600 microg misoprostol or placebo intravaginally. They were assessed the following day and administered a second dose of their allocated treatment if miscarriage was not complete. Those not successful after two doses were seen on day 7, and, if miscarriage was not complete, an ERPC was performed.\n The success rate of medical management was 88.5% (46/52) compared with 44.2% (23/52) for expectant management. There was no significant difference in success rate (100 versus 85.7%) in women treated with an incomplete miscarriage. Women with early pregnancy failure had a success rate of 87% with misoprostol compared with 29% with expectant management [odds ratio (OR) 15.96; 95% confidence interval (CI) 5.26, 48.37]. The complete miscarriage rate was achieved quicker in the medical group than the expectant group by day 1 (32.7 versus 5.8%) and by day 2 (73.1 versus 13.5%) of treatment. There were no differences in side-effects, bleeding duration, analgesia use, pain score and satisfaction with treatment. Women in the expectant group made more outpatient visits (5.06 versus 4.44%; OR = -0.62, 95% CI -1.04, -0.19). More women in the medical group (90.4 versus 73.1%; OR 1.26, 95% CI 1.05, 1.50) would elect the same treatment in the future.\n Medical management using 600 microg misoprostol vaginally is more effective than expectant management of early pregnancy failure. Misoprostol did not increase the side-effect profile and patient acceptability was superior to expectant management.", "The objective of this work was to compare the efficacy of 50 and 100 microg of misoprostol administered intravaginally for cervical ripening and labor induction. Ninety-five patients were randomly assigned to receive 50 microg (n=48) or 100 microg (n=47) of misoprostol. The primary measures in this study were cesarean section rate, time from induction to delivery, need for oxytocin use, rate of uterine hyperstimulation and tachysystoles, proportion of fetal distress and neonatal Apgar score. The interval from first dose of prostaglandin to delivery was significantly shorter in the 100 ,g-group (p < 0.05). The use of oxytocin augmentation was significantly higher in the 50 microg-group (64.6% vs. 31.9%). There were 9 cases (18.8%) of tachysystole in the 50-microg group and 12 cases (25.5%) in the 100 microg-group (p NS). The cesarean section rate was double in the 100 microg-group and the difference was statically significant (p < 0.05). There was no report of uterine rupture. It can be concluded that 50 microg of misoprostol applied in the posterior vaginal fornix every 4 hours is an effective dosage for labor induction and has less adverse effects and complications than the 100 microg dose.", "To evaluate the efficacy of methyldopa in the treatment of mild pre-eclampsia, to prevent its progress and to investigate its effect on the pregnancy outcomes.\n Randomised clinical trial.\n Wad Medani Hospital in the central Sudan.\n Seventy primigravidae with single, alive baby of 28-36 weeks gestational age suffering from true mild pre-eclampsia were enrolled. The patients were randomised in two groups, treatment group who received methyldopa 750-4000 mg/day (n=34) and a control group who received no treatment (n=36). All the (treatment and control) patients were drug followed as in-patients till the delivery, seen with their babies on the days 7, 42 after the delivery.\n The outcomes examined were, rise of the diastolic blood pressure to 110 mm Hg or more, occurrence of imminent eclampsia or the eclampsia, if the maturity could be achieved, occurrence of intrauterine growth retardation, abruptio placentae, mode of delivery, birth weight, placental weight, perinatal death, Apgar score and referral of the babies to the pediatrician.\n Three out of 34 (8.8%) of the treatment group had a rise in the diastolic blood pressure of 110 mm Hg, 18/36 (50%) of the control had a rise in the diastolic blood pressure of 110 mmHg (p < 0.05). Three out of thirty four (8.8%) of the treatment group developed imminent eclampsia, while 10/36 (27.8) of the control group developed imminent eclampsia (p < 0.05). The maturity was achieved in 82.3% and 88.8% of the treatment and the control, respectively (p > 0.05). There were ten (14.2%) perinatal deaths, four of them in the treatment group, while six in the control (p > 0.05). There was no difference regarding birth weight, occurrence of intrauterine growth retardation, placental weight, mode of delivery, Apgar score, referral of the babies to the paediatrician. No patient developed eclampsia or abruptio placenta; there was no maternal death in both groups.\n Methyldopa can prevent the progress of the mild pre-eclampsia to severe pre-eclampsia, without affecting the maturity, birthweight or the neonatal outcomes.", "The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population.\n A randomized, double-blind, placebo-controlled study included 142 high-risk singleton pregnancies. Progesterone (100 mg) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes, between 24 and 34 weeks of gestation. Progesterone (n = 72) and placebo (n = 70) groups were compared for epidemiologic characteristics, uterine contraction frequency, and incidence of preterm birth. Data were compared by chi(2) analysis and Fisher exact test.\n The preterm birth rate was 21.1% (30/142). Differences in uterine activity were found between the progesterone and placebo groups (23.6% vs 54.3%, respectively; P <.05) and in preterm birth between progesterone and placebo (13.8% vs 28.5%, respectively; P <.05). More women were delivered before 34 weeks in the placebo group (18.5%) than in the progesterone group (2.7%) (P <.05).\n Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity." ]

[ "12771264", "11291531", "8866496", "7912819", "3546605", "17721754", "3791601", "12865605", "14741060" ]

[ "Idebenone treatment in Friedreich patients: one-year-long randomized placebo-controlled trial.", "Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol.", "A controlled trial of idebenone in Huntington's disease.", "Clinical, EEG mapping and psychometric studies in negative schizophrenia: comparative trials with amisulpride and fluphenazine.", "A controlled trial of isoniazid therapy for action tremor in multiple sclerosis.", "Effects of rosiglitazone on plasma brain natriuretic peptide levels and myocardial performance index in patients with type 2 diabetes mellitus.", "Increased occurrence of left ventricular thrombi during early treatment with timolol in patients with acute myocardial infarction.", "Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes.", "A double-blind, placebo controlled, cross-over trial of adjunctive donepezil for cognitive impairment in schizophrenia." ]

[ "The authors carried out a 1-year, randomized, placebo-controlled trial of idebenone in 29 patients with Friedreich ataxia. They found significant reductions of interventricular septal thickness and left ventricular mass in the idebenone group vs the placebo group, with no improvement in other heart ultrasound measures or neurologic condition. The absolute cardiac changes were modest, but the findings suggest that larger trials should assess whether idebenone reduces ventricular hypertrophy in patients with Friedreich ataxia.", "To assess the efficacy of quetiapine, a recently introduced second generation antipsychotic medication, in reducing cognitive impairment in patients with schizophrenia.\n Prospective, randomized, double-blind clinical trial.\n 25 patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited from 3 Canadian hospitals. INTERVENTION AND OUTCOME MEASURES: After a 48-hour washout period, 25 patients with schizophrenia were randomly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms, mood and extrapyramidal side effects, as well as standardized neuropsychological measures sensitive to 6 cognitive domains: fine motor skill, attention span, verbal reasoning and fluency, visuospatial construction and fluency, executive skills and visuomotor tracking, and immediate recall of verbal and nonverbal materials. The measures were repeated 8 weeks and 6 months after treatment was initiated.\n Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine also had beneficial effects on cognitive skills, particularly verbal reasoning and fluency skills and immediate recall, with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment. Patients taking haloperidol showed improvements in general clinical status, but no specific improvements on the positive syndrome, the negative syndrome, depression ratings or cognitive skills.\n These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic.", "One hundred patients with clinically diagnosed Huntington's disease (HD) were randomized to either idebenone, an antioxidant and enhancer of oxidative metabolism, or placebo, in a 1-year, double-blind, parallel-group study aimed at slowing the rate of progression of the disease. Ninety-one patients completed the study. There were no significant differences between groups on the primary outcome measures of the Huntington's Disease Activities of Daily Living Scale (ADL-an index of functional status) and the Quantified Neurologic Examination (QNE). Sample size calculations based on progression of the ADL and QNE in this study group revealed that a larger study group is necessary to detect any differences less than an almost complete halting of the disease. This argues for multicenter efforts for future therapeutic trials in HD.", "Based on recent quantitative EEG findings of increased slow activity in negative schizophrenia indicating organicity, it was hypothesized that neuroleptics decreasing delta/theta activity should be beneficial for schizophrenics with predominantly negative symptoms. Thus, a double-blind, clinical, psychometric and neurophysiological study was carried out in 40 hospitalized patients with unproductive schizophrenia (mean age: 31 years; ICD diagnoses: 295.0, 295.1 and 295.6) who were treated randomly either with the benzamide amisulpride (AMI; n = 19) or low doses of fluphenazine (FLU; n = 21). In the first 2 weeks the daily doses were 50 mg AMI or 2 mg FLU, respectively, from the third week on up to the sixth week 100 mg AMI and 4 mg FLU. Clinical evaluations, psychometry and EEG mapping were performed on day 1 (hours 0 and 4--acute effect), on day 14 (hour 0--subacute effect) and on day 42 (hours 0 and 4--chronic and superimposed effects). Three AMI patients discontinued therapy prematurely because of productive symptoms (days 14, 28 and 35), while in the FLU group 2 patients dropped out due to depressive symptoms (days 21, 28), 1 due to productive symptoms (day 35), 1 due to ineffectiveness (day 28), and 1 because of an akinetic crisis (day 6). Statistical evaluation demonstrated a significant improvement in the AMDP apathy and Andreasen SANS score in both groups with the patients remaining severely ill as rated by the CGI. FLU-treated patients needed significantly more anticholinergic medication than the AMI-treated group. Psychometric evaluation showed in regard to the noopsyche significant improvement after subacute, chronic and superimposed AMI, while FLU-treated patients showed significant improvement only after subacute treatment. AMI was significantly superior to FLU at the hours 0 and 4 of day 42. The thymopsyche improved after subacute, chronic and superimposed administration of both compounds with a significant superiority of AMI on days 14 and 42 (4 h postdrug). EEG mapping showed a decrease of delta/theta and increase of beta activity as well as an acceleration of the centroid after acute and superimposed AMI on day 42 as compared with baseline; FLU patients exhibited a decrease of delta/theta activity and an acceleration of the total centroid too, while alpha activity was augmented and beta activity tended to be reduced. Our study demonstrated that, in addition to the new benzamide AMI, FLU in low doses may also be regarded as a neuroleptic with activating properties and may be utilized in the treatment of schizophrenics with predominantly negative symptoms.", "Ten patients with clinically definite multiple sclerosis (MS) and action tremor were treated with isoniazid (INH) in a double-blind single crossover trial. The daily dose of INH administered during the 4-week treatment phase of the trial was determined by acetylator phenotype with slow acetylators receiving 12 mg/kg per day and rapid acetylators 20 mg/kg per day. Six of eight patients who completed the trial showed clinical improvement in the postural (alternating) tremor while on INH but the degree was minimal in all cases. Results of tremograms indicated that improvement also occurred in the intentional (synchronous) component of three patients while on INH, but this did not achieve statistical significance. Cerebrospinal fluid (CSF) levels of gamma-aminobutyric acid (GABA) homocarnosine and ornithine were markedly elevated with INH therapy (providing evidence for substantial inhibition of GABA aminotransferase activity and increase in GABA in the CNS), but no correlation was found between the degree of GABA elevation in the CSF and the clinical response. Side effects were minimal and well tolerated. Although INH appears to have a limited therapeutic role, a trial is warranted in MS patients with postural tremor.", "Thiazolidinediones (TZD) have become a powerful tool for lowering insulin resistance. The problem of cardiovascular adverse events including fluid retention and risk of heart failure should be well known and recognised. We aimed to evaluate the long-term effects of rosiglitazone on cardiac function and fluid dynamics. Forty-six type 2 diabetic patients were randomised to treatment with rosiglitazone or metformin or to a control group. There are no significant differences between the groups in the duration of diabetes, HbA1c, plasma brain natriuretic peptide (BNP) levels, body mass index and myocardial performance indexes (MPIs) before the treatment. After three and six months all these parameters were repeated. Rosiglitazone increased plasma BNP levels and worsened MPIs 3 months after the start of treatment. Also left ventricular end-systolic volume increased and weight gain was observed. But these results were statistically non-significant (all p>0.05). When we continued rosiglitazone treatment to six months the increase in BNP levels became soft and statistically significant improvements were seen in MPIs (p<0.01). Also left ventricular end-systolic volume decreased significantly (p=0.004) and weight gain was stopped. In patients with type 2 diabetes, TZD treatment might have slight adverse effects on ventricular contractility and fluid dynamics at the beginning of the therapy. However, these changes seem to stabilise in the long term.", "To examine whether early intervention with timolol influences the occurrence of left ventricular thrombi in acute anterior myocardial infarction, 40 patients with acute anterior myocardial infarction admitted to hospital within 6 hr of onset of symptoms were randomly assigned to receive intravenous followed by oral timolol maleate or placebo. Five (25%) of 20 patients in the placebo group and 14 (73.7%) of 19 patients with confirmed infarction in the timolol group developed a left ventricular apical thrombus as detected by two-dimensional echocardiography from 2 to 10 days after inclusion (p less than .005). Patients received anticoagulants only after a left ventricular thrombus had been diagnosed. Only one patient with thrombus suffered peripheral embolization (timolol group). The treatment groups were comparable with respect to location of regional left ventricular dysfunction, electrocardiographic changes, and infarct size estimated by creatine kinase release. However, computer-assisted regional wall motion analysis demonstrated significantly reduced apical wall motion in the timolol group compared with the placebo group (p less than .01). Also, the mean heart rate during the first 10 days after the acute infarction was reduced by 13% in the timolol group (p less than .001). The reduction in heart rate and left ventricular apical wall motion caused by timolol in patients with acute anterior myocardial infarction may increase the occurrence of left ventricular thrombi.", "Cytidine diphosphate choline (citicoline) has been previously shown to have efficacy in reducing the functional impairments associated with acute stroke. Citicoline is thought to have neuroprotective benefits and has been used for the treatment of chronic cerebrovascular disorders, though its effectiveness has not been fully tested. This randomized, double-blind clinical trial was conducted to determine whether daily citicoline treatment improves neurocognitive and neuroimaging outcome over 12 months among patients diagnosed with vascular dementia (VaD).\n 30 patients diagnosed with VaD, based upon NINDS-AIREN and DSM-IV criteria, were randomized and treated with either 500 mg of citicoline or placebo twice per day. Patients were assessed at baseline, and at 6, and 12 months on a battery of neurocognitive tests. Neuroimaging measures of total brain volume and subcortical/periventricular hyperintensity (SH) volume on magnetic resonance imaging (MRI) were collected at baseline and the 12-month follow-up.\n The citicoline and placebo treatment groups did not differ in their neuropsychological performance at baseline and the 12-month follow-up. Significant declines in neuropsychological performance were noted, as well as significantly increased SH and reduced total brain volumes on MRI for both groups at the 12-month follow-up.\n The efficacy of long-term citicoline treatment for cognitive impairment and neuropathological decline in those patients already meeting criteria for VaD does not appear to be substantiated by the current study.\n Copyright 2003 S. Karger AG, Basel", "Although there have been several case reports suggesting the beneficial effect of acetylcholinesterase inhibitors in the cognitive deficits seen in schizophrenia, controlled studies have revealed contradictory results. The aim of this study was to investigate if donepezil could improve cognitive functions in schizophrenia. Twelve schizophrenic patients, who were diagnosed according to DSM-IV criteria and who had been on a stable dose of a high-potency typical antipsychotic for a minimum period of 3 months, participated in this 12-wk double-blind, placebo controlled, cross-over study of donepezil adjunctive treatment. Patients were randomly assigned under double-blind conditions to receive 5 mg/d donepezil or placebo for 6 wk, and then were crossed over to the alternate condition for 6 additional weeks. At baseline, 6 and 12 wk, patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, the Wechsler Memory Scale Revised (WMS-R), a test for Verbal Fluency, Trail Making Test, Parts A and B, and Wisconsin Card Sorting Test (WCST). Treatment effect was not significant in any of the cognitive measures. There were also no significant changes in the PANSS and depression scores. Nicotinic receptor desensitization may cause non-responsiveness to acetylcholine as previously suggested, but the most likely explanation appears to be that defects in other neurotransmitter systems account for the cognitive deficits seen in schizophrenic patients." ]

[ "17919621", "22554673", "12698153", "9112351", "7520105", "10755536", "9275110", "11888584", "12962761" ]

[ "A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation.", "Tacrolimus and cyclosporine have differential effects on the risk of development of bronchiolitis obliterans syndrome: results of a prospective, randomized international trial in lung transplantation.", "Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a 2-center prospective randomized trial.", "A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group.", "Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group.", "Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation.", "Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.", "Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study.", "Tacrolimus-Basiliximab versus Cyclosporine-Basiliximab in renal transplantation \"de novo\": acute rejection and complications." ]

[ "The optimal maintenance immunosuppressive regimen after lung transplantation is uncertain.\n We conducted a randomized controlled trial of tacrolimus versus cyclosporine in combination with azathioprine and prednisone after lung transplantation. Ninety adults were randomized to tacrolimus (n = 44) or cyclosporine (n = 46). The primary end point was a composite of a cumulative acute rejection A score of 3 or higher, a cumulative lymphocytic bronchitis B score of 4 or higher, or the onset of bronchiolitis obliterans syndrome (BOS) stage 0-p.\n Recipients randomized to cyclosporine were significantly more likely to develop the primary end point than those randomized to tacrolimus. During the study period, the primary end point developed in 39 of 46 cyclosporine subjects compared with 24 of 44 tacrolimus subjects (p = 0.002); acute rejection or lymphocytic bronchitis end points developed in 29 of 46 cyclosporine subjects compared with 18 of 44 tacrolimus subjects (p = 0.036). Furthermore, BOS stage 0-p was more likely to develop in the cyclosporine group than in the tacrolimus group, but this was not statistically significant (log-rank p = 0.1). In addition, there was a trend to a higher incidence of diabetes among those in the tacrolimus group, but there was no significant difference in graft survival or the total number of infections, or in the incidence of hypertension, chronic kidney disease, or cancer between the 2 groups.\n Tacrolimus is associated with a lower burden of acute rejection and lymphocytic bronchitis and a trend to a greater freedom from BOS stage 0-p than cyclosporine after lung transplantation.", "Chronic lung allograft dysfunction, which manifests as bronchiolitis obliterans syndrome (BOS), is recognized as the primary cause of morbidity and mortality after lung transplantation. In this study we assessed the efficacy and safety of two de novo immunosuppression protocols to prevent BOS.\n Our study approach was a multicenter, prospective, randomized (1:1) open-label superiority investigation of de novo tacrolimus vs cyclosporine, with both study arms given mycophenolate mofetil and prednisolone after lung transplantation. Cytolytic induction therapy was not employed. Patients were stratified at entry for cystic fibrosis. Primary outcome was incidence of BOS 3 years after transplant (intention-to-treat analysis). Secondary outcomes were survival and incidence of acute rejection, infection and other adverse events.\n Group demographic data were well matched: 110 of 124 tacrolimus vs 74 of 125 cyclosporine patients were treated per protocol (p < 0.01 by chi-square test). Cumulative incidence of BOS Grade ≥1 at 3 years was 11.6% (tacrolimus) vs 21.3% (cyclosporine) (cumulative incidence curves, p = 0.037 by Gray's test, pooled over strata). Univariate proportional sub-distribution hazards regression confirmed cyclosporine as a risk for BOS (HR 1.97, 95% CI 1.04 to 3.77, p = 0.039). Three-year cumulative incidence of acute rejection was 67.4% (tacrolimus) vs 74.9% (cyclosporine) (p = 0.118 by Gray's test). One- and 3-year survival rates were 84.6% and 78.7% (tacrolimus) vs 88.6% and 82.8% (cyclosporine) (p = 0.382 by log-rank test). Cumulative infection rates were similar (p = 0.91), but there was a trend toward new-onset renal failure with tacrolimus (p = 0.09).\n Compared with cyclosporine, de novo tacrolimus use was found to be associated with a significantly reduced risk for BOS Grade ≥1 at 3 years despite a similar rate of acute rejection. However, no survival advantage was detected.\n Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.", "Cyclosporine (INN: ciclosporin) A or tacrolimus have been used mostly in combination with azathioprine as primary immunosuppression after lung transplantation. Benefit or risk deriving from the combination with mycophenolate mofetil are yet unknown.\n In a prospective, 2-center, open randomized trial, the combination of cyclosporine A, mycophenolate mofetil, and steroids was compared with tacrolimus, mycophenolate mofetil, and steroids as primary therapy after primary lung transplantation. All patients underwent induction therapy with rabbit antithymocyte globulin for 3 days. The 2 groups were compared with regard to patient survival, freedom from acute rejection, bronchiolitis obliterans, infectious episodes, and side effects.\n Between September 1997 and April 1999, 74 lung transplant recipients were randomized to receive either cyclosporine A (n = 37) or tacrolimus (n = 37). Groups were comparable with regard to age, sex, transplant procedure, and cytomegalovirus match. Mean follow-up was 507 +/- 258 and 508 +/- 248 days, respectively. Six- and 12-month survival was similar in both groups (89% vs 84% and 82% vs 71%, respectively; P =.748 at 12 months). Two patients from the cyclosporine A group were retransplanted. Freedom from acute rejection at 6 and 12 months was comparable between groups (46% vs 51% and 35% vs 46%, respectively; P =.774 at 12 months). The mean number of treated acute rejection episodes per 100 patient-days was higher in the cyclosporine A than in the tacrolimus group, but the difference was not statistically significant (0.32 +/- 0.42 vs 0.22 +/- 0.30, respectively; P =.097). Four patients from the cyclosporine A group had to be switched to tacrolimus to control ongoing rejection, whereas no patient from the tacrolimus group had to be switched to cyclosporine A. There was a trend toward more infections (0.7 +/- 0.36 vs 0.55 +/- 0.31, P =.059) in the cyclosporine A group. New-onset diabetes mellitus was observed in the tacrolimus group only (11% vs 0%, P =.151), whereas there was a higher incidence of hypertension (60% vs 11%, P =.03) in the cyclosporine A group.\n This 2-center, prospective randomized study showed high immunosuppressive potency of both cyclosporine A and tacrolimus in combination with mycophenolate mofetil. No significant difference in incidence of acute rejection was observed between the 2 groups. Moreover, survival and incidence of infection were similar. Incidence of drug-related adverse events were similar, yet their spectrum was different.", "Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants.\n A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection.\n One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients.\n Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.", "Studies in the USA and Japan have shown that tacrolimus (FK506) is a potent immunosuppressant. To compare the efficacy and safety of tacrolimus-based and conventional cyclosporin-based immunosuppressive regimens we recruited 545 liver transplant recipients from eight European centres into a randomised open trial. Analysis of the data at 12 months post-transplant showed that tacrolimus was associated with a significant reduction in acute, refractory acute, and chronic rejection episodes. The rates were, for acute rejection, tacrolimus 40.5% vs 49.8% cyclosporin (p = 0.040; absolute difference 9.3% [95% CI 0.9-17.8%]). For refractory acute and chronic rejections the comparisons were 0.8% vs 5.3% (p = 0.005) and 1.5% vs 5.3% (p = 0.032). There results were seen despite significantly lower corticosteroid usage. The incidence of infection was also lower in patients receiving tacrolimus. Patient and graft survival rates were not significantly different (tacrolimus 82.9% and 77.5%; cyclosporin 77.5% and 72.6%). Safety data were comparable--the most serious events being renal impairment, disturbances of glucose metabolism, and neurological complications--but these events were more common in the tacrolimus group. In this trial tacrolimus had advantages over cyclosporin in respect of lower rejection rates, even though less concurrent immunosuppression was administered.", "Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation.\n A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year.\n There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups.\n All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.", "To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection.\n A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids.\n At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment.\n The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.", "In previous comparative studies tacrolimus was superior to the standard formulation of ciclosporin in preventing acute rejection after renal transplantation. We have compared the microemulsion formulation of ciclosporin with tacrolimus in a multicentre randomised trial.\n The 6-month open study involved 560 patients in 50 European centres. 287 patients were randomly assigned tacrolimus and 273 ciclosporin microemulsion plus azathioprine and corticosteroids. The initial oral daily doses were 0.30 mg/kg for tacrolimus and 8-10 mg/kg for ciclosporin. The primary endpoint was the proportion of patients with biopsy-proven acute rejection and the time to this event.\n The two study groups were similar in terms of baseline characteristics. Three patients did not receive study treatment or did not undergo transplantation (one tacrolimus, two ciclosporin). The rate of biopsy-confirmed acute rejection was significantly lower with tacrolimus than with ciclosporin microemulsion (56 patients [19.6%] vs 101 [37.3%]; 17.7% difference [95% CI 10.3-25.1]; p<0.0001). Biopsy-confirmed corticosteroid-resistant rejection was also significantly lower with tacrolimus (27 [9.4%] vs 57 [21.0%]; 11.6% difference [5.7-17.5]; p<0.0001). Cross-over between therapies because of biopsy-proven rejection was judged necessary in one of 286 (0.3%) tacrolimus-group patients and 27 of 271 (10.0%) ciclosporin-group patients (p<0.0001). There were no significant differences in survival of patients or grafts or in renal function. The overall frequency of adverse events was similar in the two groups, though hypertension and hypercholesterolaemia were more common in the ciclosporin group and tremor and hypomagnesaemia were more frequent in the tacrolimus group.\n Tacrolimus was significantly more effective than ciclosporin microemulsion in preventing acute rejection after renal transplantation and had a superior cardiovascular-risk profile.", "Optimal immunosuppression is essential to maintain kidney allograft viability but minimizing toxicity is also fundamental.\n This article compares immunosuppressants, corticosteroids, cyclosporine, tacrolimus, and basiliximab, which are used in the treatment regimens for renal transplantation. The analyses evaluated their effectiveness to prevent acute rejection episodes and to reduce the appearance of other complications, mainly infectious disease complications.\n Ninety-five patients were analysed during the first year after primary renal transplantation. These patients were included in a random way in 3 different groups according to the immunosuppressant drug therapy: Group I (35 patients) received corticosteroids + CsA; Group II (35 patients) received corticosteroids + CsA + Basiliximab; Group III (25 patients) received corticosteroids + Tacrolimus + Basiliximab.\n Among the 95 patients, 9 presented with an acute rejection episode in Group I. None in Group II, and one in group III. With reference to the infectious disease complications, the incidence of oral herpes was one case in Group I, 4 cases in Group II, and 2 cases in group III.\n Treatment with Basiliximab produced a significantly lower incidence of acute rejection cases and an increase in infectious disease complications, such as lip herpes." ]

[ "15121569", "11166751", "12635758", "16241013", "20027030", "11287024", "17628562", "10929961", "12678150" ]

[ "Paracervical block in incomplete abortion using manual vacuum aspiration: randomized clinical trial.", "Comparison of paracervical block techniques during first trimester pregnancy termination.", "Pain relief using paracervical block in patients undergoing manual vacuum aspiration of uterus.", "Randomized controlled trial of mefenamic acid vs paracervical block for relief of pain for outpatient uterine curettage.", "Paracervical block efficacy in office hysteroscopic sterilization: a randomized controlled trial.", "Paracervical block with and without conscious sedation: a comparison of the pain levels during egg collection and the postoperative side effects.", "A randomized comparison of different methods of analgesia in abortion using manual vacuum aspiration.", "Feasibility and pain control in outpatient hysteroscopy in postmenopausal women: a randomized trial.", "Double-blind randomized comparison of xylocaine and saline in paracervical block for diagnostic fractional curettage." ]

[ "To estimate the effectiveness of paracervical block in controlling pain among women treated with manual vacuum aspiration for an incomplete abortion\n A randomized clinical trial was conducted at Nuestra Señora de Altagracia, a maternal and perinatal referral hospital in the Dominican Republic. The sample size was based on a clinical difference of 1.5 points in the level of pain measured with the visual analog scale using 90% power and a sampling error of 0.04. Women who were at 12 weeks of gestation or less with an incomplete abortion were eligible to participate. They were randomly assigned to receive either the standard treatment of care (manual vacuum aspiration for uterine evacuation with psychological support but no paracervical block) or manual vacuum aspiration treatment with psychological support and paracervical block using 1.0% lidocaine. Patients with active infections, severe illnesses, psychiatric disorders, or allergies to lidocaine were excluded. Intraoperative pain as reported by the women and as documented by an external observer was measured.\n Although the paracervical block technique used showed a slight reduction in severe pain, there were no clinically or statistically significant differences in intraoperative pain between the 2 groups (relative risk 0.73; 95% confidence interval 0.43, 1.23) with 50% of all patients registering 7 or higher score on a visual analog pain scale of 0-10. However, statistically significant differences were found in each group when comparing the level of preoperative and intraoperative pain described by the patient (P <.001). The manual vacuum aspiration technique and the paracervical block were not accompanied by complications.\n The paracervical block technique used in this study along with psychological support was comparable with pain control using psychological support alone; neither pain management regimen provided sufficient pain control. It is recommended that randomized comparative studies be designed to determine the effectiveness of other paracervical block techniques and the efficacy of the use of analgesics in patients suffering from incomplete abortion treated with manual vacuum aspiration.", "To determine whether variations in chloroprocaine placement in paracervical blocks influence effectiveness, whether chloroprocaine is superior to saline, and what factors influence pain perception.\n Eighty-two women undergoing first trimester aspiration abortions were randomized to receive 1% chloroprocaine or saline at 3-5-7-9 or 4-8 o'clock positions. Using a 0--10 scale, women rated anxiety, dysmenorrhea, and pain associated with laminaria insertion, paracervical block, and aspiration.\n All four groups were similar in medical and demographic characteristics. Injection position did not influence pain ratings, but women who received chloroprocaine had less pain than those who received saline (6.3+/-2.3 vs. 7.8+/-2.0, P=0.002). Paracervical pain and dysmenorrhea were independently associated with aspiration pain scores (respective regression coefficients 0.49 and 0.26, P<0.008).\n There is no advantage to using a four-site paracervical block over a two-site technique, but chloroprocaine is superior to saline. Paracervical block may not provide adequate anesthesia during first trimester abortion, especially for women with significant dysmenorrhea.", "To evaluate pain relief using paracervical nerve block with 1% lignocaine injection in patients undergoing uterine evacuation by Manual Vacuum Aspiration (MVA) for the treatment of incomplete abortion.\n A randomized double blind clinical trial.\n Marie Stopes Health Centre, Nairobi.\n One hundred and forty two patients were recruited between September and October 1997. The intervention was random assignment to the study group (paracervical block with 1% lignocaine) or the placebo group (paracervical block with sterile water for injection). Intra and post operative assessment of pain was made using McGills and facial expression scales.\n The untreated group experienced significantly more pain than the treated group, especially lower abdominal pain and backache. The pain was especially marked intraoperatively, less so 30 minutes post-operatively.\n Based on the findings of this study, any patient going for manual vacuum aspiration for the treatment of incomplete abortion should be given Paracervical block as it is cost effective, easy to perform and with less side effects.", "To compare the efficacy of mefenamic acid vs paracervical block for pain relief during and after fractional curettage.\n Between January 1 and July 31, 2002, the authors enrolled 87 patients with abnormal uterine bleeding, who requested fractional curettage at the Outpatient Gynecologic Clinic, Srinagarind Hospital, Khon Kaen University. A simple randomization procedure was used to distribute the patients into a control group comprising 44 patients given a paracervical block and a treatment group comprising 43 patients given mefenamic acid (500 mg) 2 hours before starting the procedure.\n Pain was scored using a visual analogue scale (VAS range, 0 to 10).\n The median pain scores of the treatment types during endocervical, endometrial, immediately after, and 30 minutes after, fractional curettage were 2.5 vs 3.0 (p = 0.42), 6.5 vs 7.5 (p = 0.19), 4.0 vs 3.5 (p = 0.20) and 1.5 vs 1.0 (p = 0.17), respectively. The rate of complications was 6.8% (3 in 44) in the paracervical lignocaine injection group.\n The efficacy of pain relief for fractional curettage using oral mefenamic acid (500 mg) two hours before the procedure was not statistically different from the paracervical block, but there were fewer side effects. Mefenamic acid should be considered an alternate pain relief during fractional curettage.", "To estimate the efficacy of paracervical block compared with saline for pain relief during office hysteroscopic sterilization.\n This study was a randomized, placebo-controlled study of women desiring hysteroscopic sterilization. A paracervical block of 1% lidocaine or normal saline was administered before office hysteroscopic sterilization. Patients and investigators were blinded to assignments. A pre hoc power analysis determined that 40 women would be required per arm to detect a difference of 0.9 cm on a visual analog scale. Pain was recorded on a visual analog scale at multiple procedure time points. Individualized standardized pain scores were constructed by weighted reporting of objective and subjective sensation.\n A total of 103 consecutive women were eligible, and 80 women were randomized, with 40 per group. Thirty-seven (93%) in each group had successful placement. The lidocaine group showed significantly lower pain scores for tenaculum placement (mean+/-standard deviation: 0.97+/-1.28 compared with 3.00+/-2.41, P<.001) traversing the external cervical os (1.46+/-1.71 compared with 3.77+/-2.68, P<.001) and internal os (1.79+/-2.11 compared with 4.10+/-2.77, P<.001). There was no significant observed difference with device placement in tubal ostium (3.15+/-2.69 compared with 3.74+/-2.73, P=.33). Multivariable linear regression analysis demonstrated a relationship of pain to procedural time (P=.047) and to group assignment (P<.01).\n Paracervical block with 1% lidocaine provides effective pain relief for cervical manipulations during office hysteroscopic sterilization, but does not reduce the pain associated with upper uterine/tubal manipulation when placing the devices.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00811187.\n I.", "To compare the pain levels during egg collection and the subsequent postoperative side effects in patients receiving a paracervical block (PCB) with and without conscious sedation.\n A prospective, randomized, double-blind, and placebo-controlled study.\n A tertiary assisted reproduction unit.\n 150 patients undergoing egg collection.\n Randomized to receive PCB only (control group) and PCB in conjunction with conscious sedation (sedation group).\n Vaginal and abdominal pain levels; severity of postoperative side effects.\n The median pain levels during vaginal punctures were 12.0 (2.5th--97.5th centiles: 0--84.3) and 30.0 (2.5th--97.5th centiles: 0--100) in the sedation and placebo groups, respectively. The corresponding median abdominal pain levels were 16.5 (2.5th--97.5th centiles: 0--100) and 43.0 (2.5th--97.5th centiles: 0--100). The pain levels were significantly higher in the placebo group than the sedation group. There were no significant differences between the two groups in the severity of nausea, vomiting, dizziness, and drowsiness.\n Patients who received only a PCB during the egg collection experienced 2.5 times higher levels of vaginal and abdominal pain as compared to those who received both PCB and conscious sedation. The use of PCB along is not recommended for all patients but it may be considered with selected patients after they have been given extensive counseling.", "To estimate the effectiveness of different methods of analgesia among women treated with manual vacuum aspiration for spontaneous abortion.\n The 113 patients diagnosed with incomplete abortion and considered candidates for manual vacuum aspiration were randomly assigned to 3 groups of analgesic administration: diclofenac plus paracervical block; meperidine plus diclofenac; and meperidine alone. Pain levels were evaluated using the Wong Scale of Pain.\n The mean pain scores for the three groups were: diclofenac and paracervical block 5.4; meperidine plus diclofenac 5.0; meperidine 5.7 (P=0.57). Analysis of pain using the levels mild (0-3), moderate (4-6), and severe (7-10) showed no statistical significance among the 3 groups of analgesics. Adverse effects were more common in the groups using analgesia containing meperidine.\n There was no significant difference between the analgesics used among the 3 groups. Most of the patients, regardless of the analgesic used, reported moderate pain.", "Three methods of diagnostic hysteroscopy have been tested for both women's compliance and feasibility of procedures in postmenopause.\n Three hundred and sixty-two postmenopausal women were enrolled in a three-arm study: 5 mm diagnostic sheath (Group 1, 119 women), 5 mm sheath with paracervical block (Group 2, 121 women), and 3.5 mm sheath (Group 3, 121 women). CO2 was the distention medium. Both feasibility of hysteroscopy (procedures failed due to stenosis or incomplete distention of cavity) and discomfort of women have been recorded. Pain perception has been measured on a visual numerical rating scale. Statistical analysis was performed by t-test for unpaired samples and chi-square test.\n Paracervical block was per se painful in 18.2% and bleeding from injection site occurred in 38.8%. Hysteroscopy failure due to stenosis occurred in 9%, 10% and 0.4% of the three groups respectively (p<0.01). Intolerable pain was reported by 17% of women in Group 1, 6% in Group 2 (p<0.05) and in none of Group 3 (p<0.01). Pain score improved from Group 1 to Group 3 (p<0.01). Hysteroscopy was incomplete because of gas leakage in 1.7% of both Group 1 and 2 and in 13.2% of Group 3 (p<0.01).\n Pain perception in postmenopausal women was reduced when paracervical block was used, but discomfort was even less with the narrow sheath hysteroscope. The narrow sheath will expose to a high percentage of inconclusive procedures but it can be overcome by changing to the large sheath hysteroscope without affecting patient pain perception.", "Comparative study of the level of the reported pain between patients who received xylocaine and normal saline for paracervical block during fractional curettage was carried out in 70 patients in a double blind randomized controlled trial. One group of patients received xylocaine for paracervical block just before the procedure was performed while the other group received normal saline in the same manner. Self-reported pain intensity using visual analog scale was assessed at four time points including the first time point when Allis tissue forceps was applied on the cervix, the second and third time points when curettage was done on the endocervix and in the endometrial cavity respectively. The last time point was evaluated at 30 minutes after the procedure. The results of the study revealed pain occurring in patients in the normal saline group was more severe than those in the xylocaine group with statistically significant difference at the second time point (visual analog scale 4.80 +/- 2.7 in the normal saline group compared to 3.20 +/- 2.4 in the xylocaine group, p < 0.05) and third time point (visual analog scale 8.17 +/- 2.0 in the normal saline group compared to 4.94 +/- 3.1 in the xylocaine group, p < 0.05 ). On the contrary, pain occurring in patients in the normal saline group and xylocaine group was not statistically significantly different at the first time point (visual analog scale 3.62 +/- 2.7 in the normal saline group compared to 3.97 +/- 2.8 in the xylocaine group, p > 0.05) and the fourth time point (visual analog scale 1.34 +/- 2.0 in the normal saline group compared to 1.57 +/- 2.6 in the xylocaine group, p > 0.05). Before this study, there was an idea that normal saline solution could be considered for the paracervical injection solution. The explanation for this was the local anesthetic mechanism may be from distension of nerve capsules rather than blockage of specific autonomic nerves. However, this study showed that nerve capsule distension is not the only factor for pain control in paracervical block. An analgesic agent is still an important factor." ]

[ "2082953", "6379022", "406875", "2651014", "15730352", "1418054", "18674411", "9447569", "8997547" ]

[ "Lack of efficacy of hydergine in patients with Alzheimer's disease.", "Double-blind clinical and psychologic study of ergoloid mesylates (Hydergine) in subjects with senile mental deterioration.", "Pharmacotherapy for organic brain syndrome in late life. Evaluation of an ergot derivative vs placebo.", "Ergoloid mesylates ('Hydergine') in the treatment of mental deterioration in the elderly: a 6-month double-blind, placebo-controlled trial.", "Randomized controlled pilot trial of cabergoline, hydergine and levodopa/carbidopa: Los Angeles Cocaine Rapid Efficacy Screening Trial (CREST).", "Memantine in the treatment of mild to moderate dementia syndrome. A double-blind placebo-controlled study.", "Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study.", "Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type.", "A multicenter randomized double-blind study on the efficacy and safety of nicergoline in patients with multi-infarct dementia." ]

[ "There is no effective pharmacologic treatment for Alzheimer's disease, the most common dementing illness in the United States. Hydergine, a combination of ergoloid mesylates, is the only approved medication for Alzheimer's disease, but despite widespread use its efficacy remains to be established. We conducted a clinical trial of Hydergine-LC, a newer preparation of ergoloid mesylates in the form of a liquid in a capsule (LC) that may have greater bioavailability, to determine its value in patients with Alzheimer's disease.\n Eighty older adults with probable Alzheimer's disease participated in this double-blind, placebo-controlled trial of Hydergine-LC for 24 weeks. The recommended dose of 1 mg orally three times daily was used. Cognition and behavior were evaluated before and after the trial, and the patients were monitored for adverse effects. The medication was safe and well tolerated. The Hydergine-LC group did not perform better after treatment than the placebo group on any test, and its performance was worse (P less than 0.01 and P less than 0.02, respectively) on one cognitive measure (Wechsler Adult Intelligence Scale Digit Symbol Substitution Task) and on one behavioral scale (the Geriatric Evaluation by Relatives Rating Instrument).\n Hydergine-LC appears to be ineffective as a treatment for Alzheimer's disease.", "A double-blind study of 24 weeks' duration was conducted to investigate the effects of ergoloid mesylates (Hydergine) on symptoms of senile mental deterioration. Fifty-eight residents of old people's homes were included in the trial. Thirty were treated with ergoloid mesylates and 28 with placebo, and the effects of treatment were determined by means of medical and psychological examinations. On the Sandoz Clinical Assessment Geriatric Scale, the group receiving ergoloid mesylates showed significant improvement in all items. The group receiving placebo showed slight deterioration. Psychological examination showed that no changes were observed for either group in quantitative psychometric test results, although qualitative aspects of performance such as attention and concentration did improve. There was a close correlation between improved cognitive function scores on the SCAG and improved evaluations of behavior during the psychological examinations. There were marked individual differences in the degrees of improvement.", "Evaluation of treatment modalities, including pharmacotherapy, for organic brain syndrome (OBS) has been difficult because of sampling and methodological problems, and comparisons of research studies are all but impossible. In this study, an ergot derivative, a combination of dihydroergocornine mesylate, dihydroergocristine mesylate, and dihydroergokryptine mesylate (Hydergine) was compared with placebo, using a double-blind technique in a sample of nursing home residents with evidence of OBS. An 18-category symptom rating scale was used for periodic assessment over a six-month interval. Comparisons of the two groups of subjects disclosed that the Hydergine-treated group showed statistically significantly more improvement in most of the variables measured, especially during the last three months of treatment. Furthermore, sophisticated analysis revealed that positive changes in cognitive function cannot be accounted for as a mere reflection, or \"halo\" effect, associated with improved mood and general sense of well-being.", "A double-blind, placebo-controlled trial was carried out in 97 elderly patients with age-related mental deterioration to assess the efficacy of ergoloid mesylates in improving their symptoms. Patients were allocated at random to receive either 4.5 mg ergoloid mesylates per day or a matching placebo tablet and were followed-up for 6 months after the start of treatment. Clinical examinations were performed by the doctor, using the EACG rating scale (a French version of the Sandoz Clinical Assessment Geriatric scale), and by the nurse, using the NOSIE scale, when patients entered the trial and repeated after 2, 4 and 6 months. Changes in the factors (symptom groups) covered by these scales were subjected to statistical analysis. After 6-months' treatment, a statistically significant difference in favour of the ergoloid mesylates group was observed for cognitive deficits (p less than 0.05), anxiety and mood depression (p less than 0.01), unsociability (p less than 0.01), retardation (p less than 0.05) and irritability (p less than 0.001). Treatment was very well tolerated. It was also observed that there was a progressive increase in efficacy throughout the trial; this indicates that treatment with ergoloid mesylates in patients with mental deterioration should be long-term.", "This study tested three dopaminergic medications against a common unmatched placebo condition: hydergine 1 mg three times daily (n = 15); levodopa/carbidopa 25/100 mg three times daily (n = 15); cabergoline 0.5 mg per week (n = 15); and placebo three times daily (n = 15) as potential pharmacotherapies for cocaine dependence.\n The four-parallel group, Cocaine Rapid Efficacy Screening Trial (CREST) design featured a 2-week baseline period followed by randomization to an 8-week medication condition that included 1 hour per week of cognitive behavioral drug counseling. A safety evaluation was conducted 4 weeks after termination.\n Outcomes included cocaine metabolites measured in urine, retention and self-reports for drug use, cocaine craving, clinical improvement, mood and HIV risk behaviors.\n Participants assigned to receive cabergoline provided more urine samples negative for cocaine metabolites (42.4%) than those assigned to receive placebo (25.0%), a statistically significant difference after controlling for baseline differences in self-reported cocaine use (F = 2.95, df = 3; P = 0.05). Cabergoline-treated participants demonstrated a significant improvement over placebo from baseline to week 8 when measured using the Addiction Severity Index (ASI) employment subscale (overall change = - 0.09, SD = 0.10, t = 2.36, P < 0.05). Safety and adverse event measures showed similar rates and types of complaints by treatment condition.\n These results, combined with the apparent safety of cabergoline when used with this population, provide empirical support for conducting a larger study of the medication.", "The efficacy and the tolerability of memantine (1-amino-3,5-dimethyladamantane hydrochloride, Akatinol Memantine, CAS 41100-52-1) were investigated in patients with mild to moderate dementia syndrome in a randomized two-centre placebo-controlled clinical study. The test substance was administered at a dose of 10 mg/d from day 1 to day 3 and then at a dose of 2 x 10 mg/d from day 4 to the end of treatment after 42 days. Altogether, 88 patients were recruited to the study; their average age was 71.5 years. The efficacy of memantine was judged on the basis of the baseline/6 week differences in the total sum scores of the Clinical Assessment Geriatric Scale (SCAG), the Gottfries-Bräne-Steen Scale (GBS), the SCAG and GBS subscales and the global assessment of the change in the patient's condition. The effects of memantine on performance were studied with the aid of psychomotor tests and a behaviour investigation relating to activities of daily living (ADL). The tolerability of memantine was assessed on the basis of the doctor's global assessment and of entries on structured documentation forms (DOTES/TWIS). Further safety parameters--in the form of clinicochemical tests and measurements of blood pressure and heart rate--were also monitored during the study. On both the psychopathological measurement level (SCAG, global assessment of the change in the patient's condition) and the behavioural level (GBS), confirmatory statistical analysis brought to light significant differences between memantine and placebo (p less than or equal to 0.05), these differences showing a superiority of memantine. The tolerability of memantine was good in the main. The observed adverse reactions were not serious and, except in 3 patients, were rated as causing little or no impairment. The present clinical study demonstrates the efficacy of memantine in patients suffering from mostly moderate dementia syndrome. Clinical and statistically relevant improvements in the dementia-induced disturbances were found on the both the psychopathological level (SCAG, CGI) and the behavioural level (GBS). On the performance level also, the ADL behaviour investigation detected a highly significant improvement in the quality of performance of instrumented activities of daily living under memantine. Also the time taken to carry out these tasks was significantly reduced in comparison with placebo.", "The aim was to evaluate the efficacy, safety and tolerability of rivastigmine capsules in patients diagnosed with probable vascular dementia (VaD).\n VantagE (Vascular Dementia trial studying Exelon) was a 24-week, multicentre, double-blind study. VaD patients aged 50-85 years were randomized to rivastigmine capsules (3-12 mg/day) or placebo. Efficacy assessments included global and cognitive performances, activities of daily living and neuropsychiatric symptoms. Adverse events were recorded. Additional exploratory analyses determined whether heterogeneity in pathologies and symptoms extended to differential treatment effects.\n NCT00099216.\n 710 patients were randomized. Rivastigmine demonstrated superiority over placebo on three measures of cognitive performance (Vascular Dementia Assessment Scale, Alzheimer's Disease Assessment Scale cognitive subscale, Mini-Mental State Examination; all p< or = 0.05, intent-to-treat population [ITT]), but not other outcomes. Predominant adverse events were nausea and vomiting. Exploratory analyses indicated that older patients (> or =75 years old), assumed more likely to also have Alzheimer's disease (AD) pathology, demonstrated significant cognitive responses to rivastigmine and a safety profile similar to that seen in AD patients. Younger patients, assumed less likely to have concomitant AD pathology, showed no efficacy response and were associated with slight elevations of blood pressure, cerebrovascular accidents and mortality. Rivastigmine-placebo differences in patients with, versus those without, medial temporal atrophy (also suggestive of concomitant AD) showed a numerical difference similar to that seen between the older versus younger patients, but did not attain statistical significance.\n Consistent with trials evaluating other cholinesterase inhibitors, rivastigmine did not provide consistent efficacy in probable VaD. The efficacy apparent on cognitive outcomes was derived from effects in older patients likely to have concomitant Alzheimer pathology. This is supportive of an existing argument that the putative cholinergic deficit in VaD reflects the presence of concomitant Alzheimer pathology.", "Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo bilabo special extract EGb 761 (Tebonin forte, manufactured by Dr Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the, S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size.", "A 6-month double-blind, randomized, placebo-controlled clinical trial preceded by a 3-week single-blind, washout/run-in placebo phase was performed in male and female patients, 55-85 years of age with a clinical diagnosis of mild to moderate multi-infarct dementia according to DSM-III to evaluate the therapeutic efficacy and safety of nicergoline 30 mg b.i.d. Primary endpoints for efficacy were the changes in the Sandoz Clinical Assessment Geriatric Scale (SCAG) and Mini-Mental State Examination (MMSE) scores at the end of the treatment with respect to baseline. Secondary endpoints were Clinical Global Impression, 3 subtests of the Weschsler Adult Intelligence Scale and Blessed A scale for activities of daily living, and all endpoints in 2-month intervals. A total of 252 patients were screened, 136 patients entered the double-blind phase and were evaluated as intent-to-treat (ITT) patients. Fifteen patients were excluded from the efficacy analyses of valid cases (VC) due to protocol violations or because they dropped out of the study prematurely. Confirmatory efficacy analysis after 6 months of treatment revealed superiority of nicergoline treatment with p < 0.01 for both SCAG and MMSE scores (ITT and VC). Subsequent descriptive efficacy analysis resulted in significant differences in favor of nicergoline, in the majority of cases as early as 2 months after start of treatment. Nicergoline was well tolerated and a similar number of adverse events were observed in both the placebo and the nicergoline group." ]

[ "19012818", "11483144", "2016227", "11270920", "11191692", "10714046", "12233989", "16972117", "10591283" ]

[ "Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.", "Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder.", "Additive effects of psychostimulants, parent training, and self-control therapy with ADHD children.", "Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder.", "Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults.", "Imipramine plus cognitive-behavioral therapy in the treatment of school refusal.", "Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence.", "Does brief, clinically based, intensive multimodal behavior therapy enhance the effects of methylphenidate in children with ADHD?", "A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD." ]

[ "To evaluate the efficacy and safety of 30, 50, and 70 mg/day lisdexamfetamine dimesylate compared with placebo in adults with attention-deficit/hyperactivity disorder (ADHD).\n Following a 7- to 28-day washout, 420 adults aged 18 to 55 years with moderate to severe ADHD (DSM-IV-TR criteria) were treated with 30, 50, or 70 mg/day lisdexamfetamine or placebo, respectively, for 4 weeks (N = 119, 117, 122, and 62, respectively). The 50- and 70- mg/day groups underwent forced-dose titration. The primary efficacy measure was the clinician-determined ADHD Rating Scale (ADHD-RS) total score. The study was conducted from May 2006 to November 2006.\n Treatment groups were well matched at baseline, including in ADHD-RS scores. At endpoint, changes in ADHD-RS scores were significantly greater for each lisdexamfetamine dose than for placebo (placebo = -8.2, 30 mg/day lisdexamfetamine = -16.2, 50 mg/day lisdexamfetamine = -17.4, 70 mg/day lisdexamfetamine = -18.6; all p < .0001 vs. placebo), with no differences between doses. Significant differences relative to placebo were observed in each lisdexamfetamine group, beginning at week 1 and for each week throughout. The percentage of subjects who improved (Clinical Global Impressions-Improvement scale rating < or = 2) was significantly greater for each lisdexamfetamine dose than for placebo at each week and at endpoint (placebo = 29%, 30 mg/day lisdexamfetamine = 57%, 50 mg/day lisdexamfetamine = 62%, 70 mg/day lisdexamfetamine = 61%; all p < .01). Adverse events were generally mild and included dry mouth, decreased appetite, and insomnia.\n All 3 lisdexamfetamine doses were significantly more effective than placebo in the treatment of adults with ADHD, with improvements noted within 1 week. Lisdexamfetamine was generally well tolerated by these patients.\n Copyright 2008 Physicians Postgraduate Press, Inc.", "We report on a controlled trial of a mixed amphetamine salts compound (Adderall, dextroamphetamine sulfate, dextro-, levoamphetamine sulfate, dextroamphetamine aspartate, levoamphetamine aspartate, and dextroamphetamine saccharate) in the treatment of adult attention-deficit/hyperactivity disorder (ADHD).\n This was a 7-week, randomized, double-blind, placebo-controlled, crossover study of Adderall in 27 well-characterized adults satisfying full DSM-IV criteria for ADHD of childhood onset and persistent symptoms into adulthood. Medication was titrated up to 30 mg twice a day. Outcome measures included the ADHD Rating Scale and the Clinical Global Impression Score. Comorbid psychiatric disorders were assessed to test for potential effects on treatment outcome.\n Treatment with Adderall at an average oral dose of 54 mg (administered in 2 daily doses) was effective and well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall (42% decrease on the ADHD Rating Scale, P<.001), and sufficiently robust to be detectable in a parallel groups comparison restricted to the first 3 weeks of the protocol (P<.001). The percentage of subjects who improved (reduction in the ADHD rating scale of > or =30%) was significantly higher with Adderall treatment than with a placebo (70% vs 7%; P =.001).\n Adderall was effective and well tolerated in the short-term treatment of adults with ADHD. More work is needed to evaluate the long-term effects of Adderall, or other amphetamine compounds, in the treatment of adults with ADHD.", "Utilizing a double-blind, placebo design, the effects of a high (0.8 mg/kg) and a low (0.4 mg/kg) dose of methylphenidate alone and in combination with behavioral parent training plus child self-control instruction were evaluated with 96 attention deficit hyperactivity disorder children. No evidence of the superiority of the combined conditions relative to medication alone was found. Some limited support was found for the hypothesis that the effects of a high dose of psychostimulant medication could be achieved by combining the low dose with a behavioral intervention. The importance of the latter finding is highlighted by the fact that both the benefits and untoward effects of the psychostimulants appear to increase with the dose.", "The objective of this study was to compare the efficacy of the alpha-2a agonist guanfacine with that of dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder (ADHD). Seventeen adult outpatients who met DSM-IV criteria for ADHD participated in a double-blind, placebo-controlled, crossover study comparing drug effects on ADHD symptoms. Measures of change included the DSM-IV ADHD Behavior Checklist for Adults and the Copeland Symptom Checklist for Adult Attention Deficit Disorders. Cognitive measures of attention included the Stroop and Controlled Oral Word Association Test using the letters \"C,\" \"F,\" and \"L\" (COWAT, CFL version). For each trial, the drug was administered daily and titered up to optimal doses of maximum efficacy but with a minimum of side effects, and then data were collected. Both drugs significantly reduced ADHD symptoms on the DSM-IV Adult Behavior Checklist for Adults over placebo (p < 0.05). The Stroop Color subscale showed significant improvement for both drugs (p < 0.05), but the Color-Word measures showed significant improvement for guanfacine only (p < 0.01). The average dose of guanfacine was 1.10 (SD = 0.60), and the most common side effect of guanfacine was fatigue. No subjects discontinued drug trials. This preliminary study indicates that guanfacine may be a well-tolerated treatment option for adult ADHD.", "Our objective was to compare the efficacy of the new wake-promoting drug modafinil to that of dextroamphetamine for the treatment of attention deficit hyperactivity disorder (ADHD) in adults. Twenty-two adults who met DSM-IV criteria for ADHD participated in a randomized, double-blind, placebo-controlled, three-phase crossover study comparing placebo, modafinil, and dextroamphetamine for the treatment of ADHD. The twice-daily study medications were titrated to doses of optimum efficacy over 4-7 days and then held constant during the rest of each 2-week treatment phase. Measures of improvement included the DSM-IV ADHD Behavior Checklist for Adults, the Controlled Oral Word Association Test (COWAT, using the letters C, F, and L version), Stroop, and Digit Span (Wechsler Adult Intelligence Scale version). For the 21 (96%) completers, the mean (+/- SD) optimum doses of modafinil and dextroamphetamine were 206.8 mg/day +/- 84.9 and 21.8 mg/day +/- 8.9, respectively. Scores on the DSM-IV ADHD Checklist (p < 0.001) were significantly improved over the placebo condition following treatment with both active medications. Performance on the COWAT (p < 0.05) reached trend levels of significance. Both medications were generally well tolerated. This preliminary study suggests that modafinil may be a viable alternative to conventional stimulants for the treatment of adults with ADHD.", "To investigate the efficacy of 8 weeks of imipramine versus placebo in combination with cognitive-behavioral therapy (CBT) for the treatment of school-refusing adolescents with comorbid anxiety and major depressive disorders.\n This was a randomized, double-blind trial with 63 subjects entering the study and 47 completing. Outcome measures were weekly school attendance rates based on percentage of hours attended and anxiety and depression rating scales.\n Over the course of treatment, school attendance improved significantly for the imipramine group (z = 4.36, p < .001) but not for the placebo group (z = 1.26, not significant). School attendance of the imipramine group improved at a significantly faster rate than did that of the placebo group (z = 2.39, p = .017). Over the 8 weeks of treatment, there was a significant difference between groups on attendance after controlling for baseline attendance; mean attendance rate in the final week was 70.1% +/- 30.6% for the imipramine group and 27.6% +/- 36.1% for the placebo group (p < .001). Defining remission as 75% school attendance, 54.2% of the imipramine group met this criterion after treatment compared with only 16.7% from the placebo group (p = .007). Anxiety and depression rating scales decreased significantly across treatment for both groups, with depression on the Children's Depression Rating Scale-Revised decreasing at a significantly faster rate in the imipramine group compared with the placebo group (z = 2.08, p = .037).\n Imipramine plus CBT is significantly more efficacious than placebo plus CBT in improving school attendance and decreasing symptoms of depression in school-refusing adolescents with comorbid anxiety and depression.", "In this 12-week double-blind placebo-controlled trial of methylphenidate (MTP) versus placebo in 48 cocaine-dependent attention-deficit/hyperactivity disorder (ADHD) adults, the authors sought to determine whether MTP would be safe, control ADHD symptoms, and affect cocaine use. Efficacy indexes revealed significantly greater ADHD symptom relief in the MTP group. There were no group differences in self-reported cocaine use, urinalysis results, or cocaine craving. Because of the relatively small sample size, the results are preliminary. However, we found that MTP improved subjective reports of ADHD symptoms and did not worsen cocaine use while participants were in treatment.", "The additional value of a short-term, clinically based, intensive multimodal behavior therapy to optimally titrated methylphenidate in children with attention-deficit hyperactivity disorder (ADHD) was investigated.\n Fifty children with ADHD (ages 8-12) were randomized to treatment of methylphenidate or treatment with methylphenidate combined with 10 weeks of multimodal behavior therapy. The multimodal behavior therapy consisted of a child and parent behavioral therapy and a teacher behavioral training. Assessments included parent, teacher and child ratings of ADHD symptoms, oppositional and conduct behavior, social skills, parenting stress, anxiety and self-worth.\n Both treatment conditions yielded significant improvements on all outcome domains. No significant differences were found between both treatments.\n No evidence was found for the additive effect of multimodal behavior therapy next to optimally titrated methylphenidate.\n This study does not support the expectation that optimally dosed stimulant treated children with ADHD should routinely receive psychosocial treatment to further reduce ADHD- and related symptoms.", "Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder (ADHD), but no longer-term (i.e., >4 months) investigations have compared these 2 treatments or their combination.\n A group of 579 children with ADHD Combined Type, aged 7 to 9.9 years, were assigned to 14 months of medication management (titration followed by monthly visits); intensive behavioral treatment (parent, school, and child components, with therapist involvement gradually reduced over time); the two combined; or standard community care (treatments by community providers). Outcomes were assessed in multiple domains before and during treatment and at treatment end point (with the combined treatment and medication management groups continuing medication at all assessment points). Data were analyzed through intent-to-treat random-effects regression procedures.\n All 4 groups showed sizable reductions in symptoms over time, with significant differences among them in degrees of change. For most ADHD symptoms, children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care. Combined and medication management treatments did not differ significantly on any direct comparisons, but in several instances (oppositional/aggressive symptoms, internalizing symptoms, teacher-rated social skills, parent-child relations, and reading achievement) combined treatment proved superior to intensive behavioral treatment and/or community care while medication management did not. Study medication strategies were superior to community care treatments, despite the fact that two thirds of community-treated subjects received medication during the study period.\n For ADHD symptoms, our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication. Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms, but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes." ]