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[ "8942885", "14623704", "16243127", "17668530", "10365928", "19551353", "19588640", "16706244", "6446314" ]

[ "The efficacy of topical metronidazole in the treatment of ocular rosacea.", "A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial.", "A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea.", "Combined effect of anti-inflammatory dose doxycycline (40-mg doxycycline, usp monohydrate controlled-release capsules) and metronidazole topical gel 1% in the treatment of rosacea.", "A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea.", "Efficacy of topical cyclosporine for the treatment of ocular rosacea.", "A multicenter study of topical azelaic acid 15% gel in combination with oral doxycycline as initial therapy and azelaic acid 15% gel as maintenance monotherapy.", "Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea.", "A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea." ]

[ "The purpose of the study is to investigate the efficacy of metronidazole topical gel in the treatment of ocular rosacea.\n Ten patients with ocular rosacea were treated prospectively with lid hygiene and topical metronidazole applied to the lid margin in one eye and lid hygiene alone in the fellow eye. The treatment period was 12 weeks. A masked observer graded the ocular findings at the initial visit and at the conclusion of the treatment period. Pretreatment scores were compared with post-treatment scores with respect to ocular surface, eyelid margin, and combined eyelid plus ocular surface.\n Eight of ten treated eyes improved, whereas only five of ten control eyes improved. There was a statistically significant improvement in the eyelid score in both the treated and control groups (P = 0.003, P = 0.025, respectively), but no significant improvement in the ocular surface score in either group. When the pretreatment and post-treatment eyelid and ocular surface scores were combined, there was a significant improvement in the treated eyes but not in the control eyes (P = 0.022, P = 0.10, respectively). No adverse effects of the metronidazole treatment were encountered in this study.\n Metronidazole topical gel may be a safe and effective means of treating rosacea blepharitis.", "To compare the efficacy and safety of a novel formulation of 15% azelaic acid gel (Finacea; Berlex Laboratories, Inc, Montville, NJ) with 0.75% metronidazole gel (MetroGel; Galderma Laboratories LP, Fort Worth, Tex) as topical therapy for moderate, papulopustular facial rosacea.\n Multicenter, double-blind, randomized, parallel-group study.\n Thirteen US centers.\n A total of 251 patients with papulopustular rosacea with persistent erythema and telangiectasia.\n Patients were randomized to receive azelaic acid gel or metronidazole gel twice daily for 15 weeks.\n Nominal and percent change in inflammatory lesion count, change in erythema and telangiectasia severity ratings, investigator's global assessment of rosacea, and investigator's and patient's overall improvement ratings.\n Azelaic acid gel was superior to metronidazole gel in reduction of mean nominal lesion count (-12.9 vs -10.7, respectively) (P =.003) and mean percent decrease in inflammatory lesions (-72.7% vs -55.8%, respectively) (P<.001). With respect to erythema severity, 56% of azelaic acid gel-treated patients were rated improved vs 42% of metronidazole gel-treated patients (P =.02). The effectiveness of metronidazole gel on these variables seemed to plateau after week 8, whereas azelaic acid gel demonstrated progressive improvement through week 15. Neither treatment had a clinically appreciable effect on telangiectasia. Both the investigator's global assessment (P =.02) and overall assessment of improvement (P =.005) showed a significant therapeutic advantage for azelaic acid gel. Azelaic acid gel also scored higher on the patient's overall assessment of efficacy. Both treatments were rated as having high cosmetic acceptability. No serious or systemic treatment-related adverse events were reported in either group.\n Use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea (inflammatory lesions and erythema).", "Subantimicrobial doses of doxycycline may improve outcomes in rosacea when combined with topical metronidazole and used as maintenance monotherapy.\n The purpose of this study was to evaluate the safety and efficacy of doxycycline hyclate 20 mg (subantimicrobial dose doxycycline) administered twice daily as an adjunct to metronidazole 0.75% topical lotion in the treatment of rosacea.\n Patients received subantimicrobial doses of doxycycline twice daily plus metronidazole (n = 20) or placebo plus metronidazole (n = 20) for 12 weeks. Subantimicrobial-dose doxycycline or placebo monotherapy continued for 4 weeks. The primary efficacy measure was change from baseline in total inflammatory lesions at weeks 2 and 16.\n Total inflammatory lesions were reduced significantly (P =.048) by week 4 and by all subsequent visits in the subantimicrobial-dose doxycycline/metronidazole group compared with placebo/metronidazole. Changes from baseline increased over time and were maintained during subantimicrobial-dose doxycycline monotherapy.\n Adjunctive use of subantimicrobial dose doxycycline significantly reduced the clinical signs of rosacea compared with metronidazole alone and may be useful maintenance monotherapy.", "Research into the pathophysiology of rosacea suggests a central role for inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinases (MMPs). Effective treatments for rosacea, including topical metronidazole and systemic antibiotics, have anti-inflammatory activity, which may be more important than their antimicrobial activity in this setting. Phase III studies have substantiated the efficacy of anti-inflammatory dose doxycycline (40-mg doxycycline monohydrate controlled-release capsules) administered once daily for the treatment of inflammatory lesions of rosacea. Results of a 16-week, randomized, double-blind, placebo-controlled study of anti-inflammatory dose doxycycline plus topical metronidazole gel 1% for mild to moderate rosacea are presented here. At week 12, metronidazole was discontinued and patients continued on either placebo or doxycycline. Combination therapy significantly reduced inflammatory lesion counts as early as week 4 and through week 12 compared to topical metronidazole 1% gel monotherapy. The combined therapy appeared effective and well-tolerated.", "Although it is important for physicians to have sufficient clinical data on which to base treatment decisions, little comparative data exist regarding newer treatment modalities for rosacea.\n The goal of the study was to compare the efficacy and safety of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Parameters of patient satisfaction to treatment were also assessed.\n Forty patients with the clinical manifestation of symmetric facial rosacea were investigated in this single-center, double-blind, randomized, contralateral split-face comparison clinical trial.\n After 15 weeks of treatment, both azelaic acid and metronidazole induced significant, albeit equal reductions in the number of inflammatory lesions (pustules and papules). A significantly higher physician rating of global improvement was achieved with azelaic acid. Changes in the rosacea signs and symptoms of dryness, burning, telangiectasia, and itching were equal between treatments. A reduction in erythema tended toward significance with azelaic acid at week 15. A trace amount of stinging on application was noted with azelaic acid; however, such discomfort did not appear to concern patients because their overall impression of azelaic acid was superior to that of metronidazole.\n Azelaic acid 20% cream provides an effective and safe alternative to metronidazole 0.75% cream with the added benefit of increased patient satisfaction.", "This study was designed to compare the efficacy of cyclosporine ophthalmic emulsion 0.05% with an artificial tear solution for the treatment of rosacea-associated eyelid and corneal pathology.\n Double-masked, randomized, 3-month clinical trial of 37 patients with rosacea-associated eyelid and corneal changes (defined as lid margin telangiectasia, meibomian gland inspissation, and/or fullness of the lid margin). All findings were standardized and compared to photographs for grading.\n There was a statistically significant increase in Schirmer (with anesthesia) scores of 2.7+/-2.2 mm after 3 months of treatment in the topical cyclosporine group (P<0.001), compared with a mean decrease of -1.4+/-4.6 mm (P=0.271) in the artificial tears group. The mean tear break-up time score significantly improved in the topical cyclosporine group (mean increase of 3.56+/-1.5 seconds, P<0.001), but worsened in the control group, although this change was not significantly significant (mean decrease of -0.04+/-1.6 seconds, P=0.929). The topical cyclosporine group exhibited a significantly greater mean reduction in corneal staining scores (-1.3+/-0.53) compared with the control group (-0.2+/-0.83; between groups P<0.001). The topical cyclosporine group had a greater improvement in Ocular Surface Disease Index scores than those using artificial tears (P=0.022). Limitations of the study included an older, predominantly Caucasian patient population and short trial length.\n Topical cyclosporine 0.05% is more effective than artificial tears for the treatment of rosacea-associated lid and corneal changes.", "This two-phase, multicenter study was undertaken to examine the safety and efficacy of combination therapy with oral doxycycline and topical azelaic acid (AzA) 15% gel in moderate-to-severe papulopustular rosacea and to determine the effect of subsequent maintenance monotherapy with AzA 15% gel alone. In the initial open-label, non-randomized phase of the study, subjects (n=172) received topical AzA 15% gel and oral doxycycline (100 mg), both twice daily, for < or = 12 weeks. In the second, double-blind study phase, subjects who had initially undergone at least four weeks of combination treatment in phase 1 and who achieved > or = 75% inflammatory lesion count reduction (n=136) were randomized to receive either AzA 15% gel or its vehicle twice daily for an additional 24 weeks. Assessments of efficacy were obtained at four-week intervals throughout both phases of the study and included change in inflammatory lesion count, investigator global assessment (IGA) of rosacea severity, and separate assessments of erythema and telangiectasia severity. At the last visit for each phase of the study, the investigator and participant each rated overall improvement, with the participant rating cosmetic acceptability and the investigator rating treatment as \"success\" or \"failure\" based on IGA score. During the second phase of the trial, the rate of relapse -- defined as either a 50% deterioration in the lesion count improvement from phase 1, an increase in erythema intolerable to the subject or maintenance therapy failure as judged by the investigator and/or the subject -- was obtained. Safety assessments were conducted for both phases of the study and included analysis of adverse events (AEs) and a rating of cutaneous tolerability by the subject. By week 12 of the open-label phase of the study, 81.4% of subjects had reached a 75% or greater reduction in inflammatory lesion count, and 64% of patients achieved treatment success. During the second study phase (maintenance phase), AzA 15% gel consistently provided a better maintenance response than vehicle, with maintenance of remission in 75% of patients over the six-month duration of the maintenance phase. Additionally AzA 15% gel showed a statistically significantly lower deterioration in absolute inflammatory lesion counts than did vehicle after 8, 16, 20 and 24 weeks of maintenance therapy. No serious treatment-related AEs were encountered in the study, and 98.5% of subjects were satisfied with the local tolerability of both AzA gel and vehicle.", "Rosacea is an inflammatory dermatologic disorder characterized by the presence of facial erythema, visible blood vessels, papules, and pustules. The National Rosacea Society has established a classification system that identifies 4 distinct rosacea subtypes based on clinical presentation: erythematotelangiectatic, papulopustular, phymatous, and ocular. The goal of topical therapy for rosacea is to reduce inflammatory lesion counts; decrease intensity of erythema; and reduce symptoms such as stinging, burning, and pruritus. Metronidazole and azelaic acid are thought to reduce the inflammation associated with rosacea by inhibiting the production of reactive oxygen species produced by neutrophils. Both metronidazole 1% gel and azelaic acid 15% gel recently have been approved for the treatment of rosacea. The current study was conducted to compare the once-daily application of metronidazole 1% gel with twice-daily applications of azelaic acid 15% gel for the treatment of patients with moderate rosacea (N=160). Both treatments showed similar reductions in inflammatory lesion counts (77% for metronidazole 1% gel and 80% for azelaic acid 15% gel) and high success rates in both global severity (53.7% vs 56.4% for metronidazole 1% gel and azelaic acid 15% gel, respectively) and erythema (42.7% vs 42.3% for metronidazole 1% gel and azelaic acid 15% gel, respectively). On average, the efficacy (including reduction in erythema) of the once-daily application of metronidazole 1% gel and twice-daily applications of azelaic acid 15% gel were similar.", "Forty patients with papulo-pustular rosacea were treated for 12 weeks on a random double-blind basis either with oxytetracycline 250 mg twice daily or with metronidazole 200 mg twice daily. Both drugs produced an improvement which was greater after 12 weeks than after 6 weeks, but there was no significant difference between them. Metronidazole appears to be a safe and effective drug for the treatment of rosacea." ]

[ "19574405", "18407003", "19033146", "19025276", "12509354", "19017582", "21907496", "18236302", "10181019" ]

[ "Efficacy of a single computer-tailored e-mail for smoking cessation: results after 6 months.", "Web-based smoking-cessation programs: results of a randomized trial.", "Comparing internet assistance for smoking cessation: 13-month follow-up of a six-arm randomized controlled trial.", "Using the internet to assist smoking prevention and cessation in schools: a randomized, controlled trial.", "Design and pilot evaluation of an internet smoking cessation program.", "Comparing two web-based smoking cessation programs: randomized controlled trial.", "Efficacy of an internet program for smoking cessation during and after inpatient rehabilitation treatment: a quasi-randomized controlled trial.", "Computer-tailored smoking cessation intervention in a general population setting in Germany: outcome of a randomized controlled trial.", "Long-term effectiveness of computer-generated tailored feedback in smoking cessation." ]

[ "To date, few Internet-delivered smoking cessation interventions have been tested. This study tested the efficacy, understandability, credibility and personal relevance of an e-mail-delivered computer-tailored smoking cessation intervention. It included tailored action plan feedback, as recent studies have demonstrated the importance of planning in facilitating quitting smoking. Participants (Dutch adults) were randomly assigned to the intervention (computer-tailored e-mail; N = 224) or the control group (generic, non-tailored e-mail; N = 234). The results 6 months after baseline (N = 195) showed that significantly more participants in the intervention group reported not having smoked in the last 24 hours (21.5%) and 7 days (20.4%) in contrast with participants in the control group (9.8 and 7.8%, respectively). Intention-to-treat analyses revealed similar results, though overall lower quitting percentages. Furthermore, participants in the intervention group appreciated the computer-tailored e-mail significantly more in terms of understandability, credibility and personal relevance. Hence, the computer-tailored intervention is effective for the Dutch smoking population motivated to quit smoking. Further research is needed into the efficacy of the intervention for smokers who are not motivated to quit smoking and into the benefits of (multiple) e-mail-delivered tailored letters with tailored action plan feedback over and above tailoring without action plan feedback.", "Initial trials of web-based smoking-cessation programs have generally been promising. The active components of these programs, however, are not well understood. This study aimed to (1) identify active psychosocial and communication components of a web-based smoking-cessation intervention and (2) examine the impact of increasing the tailoring depth on smoking cessation.\n Randomized fractional factorial design.\n Two HMOs: Group Health in Washington State and Henry Ford Health System in Michigan.\n 1866 smokers.\n A web-based smoking-cessation program plus nicotine patch. Five components of the intervention were randomized using a fractional factorial design: high- versus low-depth tailored success story, outcome expectation, and efficacy expectation messages; high- versus low-personalized source; and multiple versus single exposure to the intervention components.\n Primary outcome was 7 day point-prevalence abstinence at the 6-month follow-up.\n Abstinence was most influenced by high-depth tailored success stories and a high-personalized message source. The cumulative assignment of the three tailoring depth factors also resulted in increasing the rates of 6-month cessation, demonstrating an effect of tailoring depth.\n The study identified relevant components of smoking-cessation interventions that should be generalizable to other cessation interventions. The study also demonstrated the importance of higher-depth tailoring in smoking-cessation programs. Finally, the use of a novel fractional factorial design allowed efficient examination of the study aims. The rapidly changing interfaces, software, and capabilities of eHealth are likely to require such dynamic experimental approaches to intervention discovery.", "Although many smokers seek Internet-based cessation assistance, few studies have experimentally evaluated long-term cessation rates among cigarette smokers who receive Internet assistance in quitting.\n The purpose of this study is to describe long-term smoking cessation rates associated with 6 different Internet-based cessation services and the variation among them, to test the hypothesis that interactive and tailored Internet services yield higher long-term quit rates than more static Web-posted assistance, and to explore the possible effects of level of site utilization and a self-reported indicator of depression on long-term cessation rates.\n In 2004-05, a link was placed on the American Cancer Society (ACS) website for smokers who wanted help in quitting via the Internet. The link led smokers to the QuitLink study website, where they could answer eligibility questions, provide informed consent, and complete the baseline survey. Enrolled participants were randomly assigned to receive emailed access to one of five tailored interactive sites provided by cooperating research partners or to a targeted, minimally interactive ACS site with text, photographs, and graphics providing stage-based quitting advice and peer modeling.\n 6451 of the visitors met eligibility requirements and completed consent procedures and the baseline survey. All of these smokers were randomly assigned to one of the six experimental groups. Follow-up surveys done online and via telephone interviews at approximately 13 months after randomization yielded 2468 respondents (38%) and found no significant overall quit rate differences among those assigned to the different websites (P = .15). At baseline, 1961 participants (30%) reported an indicator of depression. Post hoc analyses found that this group had significantly lower 13-month quit rates than those who did not report the indicator (all enrolled, 8% vs 12%, P < .001; followed only, 25% vs 31%, P = .003). When the 4490 participants (70%) who did not report an indicator of depression at baseline were separated for analysis, the more interactive, tailored sites, as a whole, were associated with higher quitting rates than the less interactive ACS site: 13% vs 10% (P = .04) among 4490 enrolled and 32% vs 26% (P = .06) among 1798 followed.\n These findings show that Internet assistance is attractive and potentially cost-effective and suggest that tailored, interactive websites may help cigarette smokers who do not report an indicator of depression at baseline to quit and maintain cessation.", "To evaluate the impact of a classroom-based, Web-assisted tobacco intervention addressing smoking prevention and cessation with adolescents.\n A two-group randomized control trial with 1,402 male and female students in grades 9 through 11 from 14 secondary schools in Toronto, Canada. Participants were randomly assigned to a tailored Web-assisted tobacco intervention or an interactive control condition task conducted during a single classroom session with e-mail follow-up. The cornerstone of the intervention was a five-stage interactive Web site called the Smoking Zine (http://www.smokingzine.org) integrated into a program that included a paper-based journal, a small group form of motivational interviewing, and tailored e-mails.\n Resistance to smoking, behavioral intentions to smoke, and cigarette use were assessed at baseline, postintervention, and three- and six-month follow-up. Multilevel logistic growth modeling was used to assess the effect of the intervention on change over time.\n The integrated Smoking Zine program helped smokers significantly reduce the likelihood of having high intentions to smoke and increased their likelihood of high resistance to continued cigarette use at 6 months. The intervention also significantly reduced the likelihood of heavy cigarette use adoption by nonsmokers during the study period.\n The Smoking Zine intervention provided cessation motivation for smokers most resistant to quitting at baseline and prevented nonsmoking adolescents from becoming heavy smokers at 6 months. By providing an accessible and attractive method of engaging young people in smoking prevention and cessation, this interactive and integrated program provides a novel vehicle for school- and population-level health promotion.", "Relatively little is known about how to use the Internet to promote health behavioral change. This article describes a multiple-contact Internet smoking cessation program with an 8-week web-based course, online tools for self-monitoring of behaviors, and computer-tailored e-mail messages timed to enrollees' quit efforts. In a pilot study in 49 smokers, we found that enrollees returned to the website a median of 2 times and completed an average of 2 of 8 educational modules. In follow-up, respondents (n = 26) rated e-mail and web components of the intervention as equally valuable (5.9 vs. 5.5 of 10, p = 0.44). While site had potentially important effects on smoking behaviors (34% of enrollees either quit smoking or had a 50% reduction in cigarette use), we were not able hold the interest of the majority of enrollees over the intervention period. Problems with the design of the site are discussed.", "Smoking cessation remains a significant public health problem. Innovative interventions that use the Internet have begun to emerge that offer great promise in reaching large numbers of participants and encouraging widespread behavior change. To date, the relatively few controlled trials of Web-based smoking cessation programs have been limited by short follow-up intervals.\n We describe the 6-month follow-up results of a randomized controlled trial in which participants recruited online were randomly assigned to either a Web-based smoking cessation program (Quit Smoking Network; QSN) or a Web-based exercise enhancement program (Active Lives) adapted somewhat to encourage smoking cessation.\n The study was a two-arm randomized controlled trial that compared two Web-based smoking cessation programs: (1) the QSN intervention condition presented cognitive-behavioral strategies, and (2) the Active Lives control condition provided participants with guidance in developing a physical activity program to assist them with quitting. The QSN condition provided smoking cessation information and behavior change strategies while the Active Lives condition provided participants with physical activity recommendations and goal setting. The QSN condition was designed to be more engaging (eg, it included multimedia components) and to present much greater content than is typically found in smoking cessation programs.\n Contrary to our hypotheses, no between-condition differences in smoking abstinence were found at 3- and 6-month follow-up assessments. While participants in the QSN intervention condition spent more time than controls visiting the online program, the median number of 1.0 visit in each condition and the substantial attrition (60.8% at the 6-month follow-up) indicate that participants were not as engaged as we had expected.\n Contrary to our hypothesis, our test of two Web-based smoking cessation conditions, an intervention and an attention placebo control, failed to show differences at 3- and 6-month assessments. We explored possible reasons for this finding, including limited engagement of participants and simplifying program content and architecture. Future research needs to address methods to improve participant engagement in online smoking cessation programs. Possible approaches in this regard can include new informed consent procedures that better explain the roles and responsibilities of being a research participant, new program designs that add more vitality (changing content from visit to visit), and new types of reminders pushed out to participants to encourage return visits. Simplifying program content through a combination of enhanced tailoring and information architecture also merits further research attention.", "To test the feasibility and efficacy of an internet program for smoking cessation during and after inpatient treatment in rehabilitation centers.\n A total of 7574 consecutively admitted inpatients from three German rehabilitation centers were assessed for smoking status. Daily smokers or former daily smokers who regularly used the internet and e-mail were proactively invited for study participation. Out of 749 eligible patients, 477 (64%) participated in the study and were randomly assigned to an intervention or an assessment only control group based on the calendar week of admission. Patients of the intervention group had the possibility to use an internet program for smoking cessation for a period of six months. The program provided at least one but up to seven individual counseling sessions through a computer expert system, informational websites and a message board.\n At six-months follow-up, seven-day point prevalence smoking abstinence was twice as high in the intervention group as in the control group (OR=2.0; CI 1.1-3.8; p=.02).\n Proactive recruitment of smokers in combination with the provision of an internet program for smoking cessation allow for an inexpensive and effective smoking cessation support during and after inpatient rehabilitation treatment.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "This study reports the outcome of a randomized controlled trial testing a computer-tailored smoking cessation intervention based on the transtheoretical model in a general population setting in Germany. Participants of the smoking intervention study were recruited from an existing general population health examination survey in a university hospital. The sample consisted of 611 current and former smokers at baseline, and of 485 participants in the core group of baseline daily cigarette smokers. Follow-ups were conducted 6, 12, 18, and 24 months after baseline. The intervention was designed for both current and former smokers, involved up to three individualized feedback letters, and was created using expert-system technology. Based on 7-day point-prevalence abstinence and 6-month prolonged abstinence as the outcome measures, the study identified no significant differences between the intervention and control groups. Modeling the full longitudinal data in generalized estimation equation analyses, using different nonresponse procedures, and adjusting for covariates did not alter the results. We conclude that the computer-tailored transtheoretical model-based smoking cessation intervention, as delivered in this study and in this special setting, was ineffective.", "Although tailored interventions consisting of only a few pages of information lead to more quitting than no intervention in the short term, the long-term efficacy of a single tailored intervention still has to be proven. In the present study smokers were reactively recruited and randomly allocated to one of four intervention conditions: (1) outcome information, (2) self-efficacy enhancing information, (3) both sorts of information or (4) no information. Smokers in the three experimental groups received computer-generated tailored feedback containing the condition-specific information, by mail. The results from the 14 months follow-up can be summarized as follows. Compared to the no information condition, all three experimental conditions led to significantly more smokers who had engaged in 24-h quit attempts. However, no experimental condition led to more 7-day quitting than the no information condition. With regard to continuous abstinence, the experimental condition offering a combination of outcome information and self-efficacy enhancing information had a significant effect, compared to the no information condition. It is concluded that a minimal six-page tailored intervention can be beneficial in supporting smokers to quit smoking, even after 14 months." ]

[ "17556431", "16113617", "19968378", "17984403", "9366660", "17581445", "15169696", "19880289", "9842950" ]

[ "Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial.", "A randomized effectiveness trial of brief cognitive-behavioral therapy for depressed adolescents receiving antidepressant medication.", "Randomized controlled trial of a family cognitive-behavioral preventive intervention for children of depressed parents.", "A randomized controlled trial of fluoxetine and cognitive behavioral therapy in adolescents with major depression, behavior problems, and substance use disorders.", "A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression.", "A pilot randomized controlled trial of combined trauma-focused CBT and sertraline for childhood PTSD symptoms.", "A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents.", "The effect of study sponsorship on a systematically evaluated body of evidence of head-to-head trials was modest: secondary analysis of a systematic review.", "Sertraline in children and adolescents with obsessive-compulsive disorder: a multicenter randomized controlled trial." ]

[ "To determine whether a combination of a selective serotonin reuptake inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical care is more effective in the short term than an SSRI and clinical care alone in adolescents with moderate to severe major depression.\n Pragmatic randomised controlled superiority trial.\n 6 outpatient clinics in Manchester and Cambridge.\n 208 adolescents, aged 11-17, with moderate to severe major or probable major depression who had not responded to a brief initial intervention. Adolescents with suicidality, depressive psychosis, or conduct disorder were included.\n 103 adolescents received an SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial lasted 12 weeks, followed by a 16 week maintenance phase.\n Change in score on the Health of the Nation outcome scales for children and adolescents (primary outcome) from baseline with 12 weeks as the primary and 28 weeks as the follow-up end point. Secondary measures were change in scores on the mood and feelings questionnaire, the revised children's depression rating scale, the children's global assessment scale, and the clinical global impression improvement scale.\n At 12 weeks the treatment effect for the primary outcome was -0.64 (95% confidence interval -2.54 to 1.26, P=0.50). In a longitudinal analysis, there was no difference in effectiveness of treatment for the primary (average treatment effect 0.001, -1.52 to 1.52, P=0.99) or secondary outcome measures. On average there was a decrease in suicidal thoughts and self harm. There was no evidence of a protective effect of cognitive behaviour therapy on suicidal thinking or action. By 28 weeks, 57% were much or very much improved with 20% remaining unimproved.\n For adolescents with moderate to severe major depression there is no evidence that the combination of CBT plus an SSRI in the presence of routine clinical care contributes to an improved outcome by 28 weeks compared with the provision of routine clinical care plus an SSRI alone.\n Current Controlled Trials ISRCNT 83809224.", "To test a collaborative-care, cognitive-behavioral therapy (CBT) program adjunctive to selective serotonin reuptake inhibitor (SSRI) treatment in HMO pediatric primary care.\n A randomized effectiveness trial comparing a treatment-as-usual (TAU) control condition consisting primarily of SSRI medication delivered outside the experimental protocol (n = 75) versus TAU SSRI plus brief CBT (n = 77). Participants were identified by a recent dispense of SSRI medication followed by telephone screening. Adolescents with a diagnosis of major depressive disorder (n = 152) were enrolled. The CBT program employed cognitive restructuring and/or behavioral activation training. Therapists consulted with prescribing pediatricians to improve medication adherence.\n Through 1-year follow-up, the authors found CBT advantages on the Short Form-12 Mental Component Scale (p = .04), reductions in TAU outpatient visits (p = .02), and days' supply of all medications (p = .01). No effects were detected for major depressive disorder episodes; a nonsignificant trend favoring CBT was detected on the Center for Epidemiology Depression Scale (p = .07).\n The authors detected a weak CBT effect, possibly rendered less significant by the small sample and likely attenuated by the unexpected reduction in SSRI pharmacotherapy in the CBT condition. Small, incremental improvements over monotherapy, such as observed in this study, most likely represent the new norm in adolescent depression treatment research.", "A family cognitive-behavioral preventive intervention for parents with a history of depression and their 9-15-year-old children was compared with a self-study written information condition in a randomized clinical trial (n = 111 families). Outcomes were assessed at postintervention (2 months), after completion of 4 monthly booster sessions (6 months), and at 12-month follow-up. Children were assessed by child reports on depressive symptoms, internalizing problems, and externalizing problems; by parent reports on internalizing and externalizing problems; and by child and parent reports on a standardized diagnostic interview. Parent depressive symptoms and parent episodes of major depression also were assessed. Evidence emerged for significant differences favoring the family group intervention on both child and parent outcomes; strongest effects for child outcomes were found at the 12-month assessment with medium effect sizes on most measures. Implications for the prevention of adverse outcomes in children of depressed parents are highlighted.", "To evaluate the effect of fluoxetine hydrochloride vs placebo on major depressive disorder, substance use disorder (SUD), and conduct disorder (CD) in adolescents receiving cognitive behavioral therapy (CBT) for SUD.\n Randomized controlled trial.\n A single-site study conducted between May 2001 and August 2004.\n One hundred twenty-six adolescents aged 13 to 19 years recruited from the community and meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic criteria for current major depressive disorder, lifetime CD, and at least 1 nontobacco SUD.\n Sixteen weeks of fluoxetine hydrochloride, 20 mg/d, or placebo, with CBT.\n For depression, Childhood Depression Rating Scale-Revised and Clinical Global Impression Improvement; for SUD, self-reported nontobacco substance use and urine substance use screen results in the past 30 days; and for CD, self-reported symptoms in the past 30 days.\n Fluoxetine combined with CBT had greater efficacy than did placebo and CBT according to changes on the Childhood Depression Rating Scale-Revised (effect size, 0.78) but not on the Clinical Global Impression Improvement treatment response (76% and 67%, respectively; relative risk, 1.08). There was an overall decrease in self-reported substance use (4.31 days; 95% confidence interval, 2.12-6.50) and CD symptoms (relative risk, 1.20; 95% confidence interval, 0.82-1.59), but neither difference between groups was statistically significant. The proportion of substance-free weekly urine screen results was higher in the placebo-CBT group than in the fluoxetine-CBT group (mean difference, 2.10; 95% confidence interval, 0.37-4.15).\n Fluoxetine and CBT had greater efficacy than did placebo and CBT on one but not both depression measures and was not associated with greater decline in self-reported substance use or CD symptoms. The CBT may have contributed to higher-than-expected treatment response and mixed efficacy findings, despite its focus on SUD.", "Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blind trials of antidepressants (largely tricyclic agents) have yet to reveal that any antidepressant is more effective than placebo. This article is of a randomized, double-blind, placebo-controlled trial of fluoxetine in children and adolescents with depression.\n Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic major depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks. Randomization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks, followed 1 week later by a 1-week, single-blind placebo run-in. Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children's Depression Rating Scale--Revised, a measure of the severity depressive symptoms.\n Of the 96 patients, 48 were randomized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) receiving placebo were rated \"much\" or \"very much\" improved on the Clinical Global Impressions scale at study exit (chi 2 = 5.1, df = 1, P = .02). Significant differences were also noted in weekly ratings of the Children's Depression Rating Scale--Revised after 5 weeks of treatment (using last observation carried forward). Equivalent response rates were found for patients aged 12 years and younger (n = 48) and those aged 13 years and older (n = 48). However, complete symptom remission (Children's Depression Rating Scale--Revised < or = 28) occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients.\n Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression. Complete remission of symptoms was rare.", "To examine the potential benefits of adding a selective serotonin reuptake inhibitor, sertraline, versus placebo, to trauma-focused cognitive-behavioral therapy (TF-CBT) for improving posttraumatic stress disorder and related psychological symptoms in children who have experienced sexual abuse.\n Twenty-four 10- to 17-year-old female children and adolescents and their primary caretakers were randomly assigned to receive TF-CBT + sertraline or TF-CBT + placebo for 12 weeks.\n Both groups experienced significant improvement in posttraumatic stress disorder and other clinical outcomes from pre- to posttreatment with no significant group x time differences between groups except in Child Global Assessment Scale ratings, which favored the TF-CBT + sertraline group.\n Only minimal evidence suggests a benefit to adding sertraline to TF-CBT. A drawback of adding sertraline was determining whether TF-CBT or sertraline caused clinical improvement for children with comorbid depression. Current evidence therefore supports an initial trial of TF-CBT or other evidence-supported psychotherapy for most children with PTSD symptoms before adding medication.", "Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents. The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression.\n An 8-week, randomized, double-blind, placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children (ages 7-11) and adolescents (ages 12-17) with major depressive disorder. Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Patients (N=174) were treated initially with placebo or 20 mg/day of citalopram, with an option to increase the dose to 40 mg/day at week 4 if clinically indicated. The primary outcome measure was score on the Children's Depression Rating Scale-Revised; the response criterion was defined as a score of < or =28.\n The overall mean citalopram dose was approximately 24 mg/day. Mean Children's Depression Rating Scale-Revised scores decreased significantly more from baseline in the citalopram treatment group than in the placebo treatment group, beginning at week 1 and continuing at every observation point to the end of the study (effect size=2.9). The difference in response rate at week 8 between placebo (24%) and citalopram (36%) also was statistically significant. Citalopram treatment was well tolerated. Rates of discontinuation due to adverse events were comparable in the placebo and citalopram groups (5.9% versus 5.6%, respectively). Rhinitis, nausea, and abdominal pain were the only adverse events to occur with a frequency exceeding 10% in either treatment group.\n In this population of children and adolescents, treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated.", "The objective of this study was to determine the effect of industry bias in a systematically reviewed body of evidence of head-to-head trials.\n We limited our analysis to published head-to-head randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs) identified in a comparative effectiveness review. Two reviewers independently determined the status of funding for each trial. We classified drugs into one of two groups: (1) drugs associated with the funding source and (2) drugs not associated with the funding source. To determine the effect of any underlying industry bias, we conducted relative-benefit meta-analyses comparing the response rates of drugs when associated with the funding source with response rates of the same drugs when not associated with the funding source.\n Thirteen out of 20 studies (65%) numerically favored drugs associated with the funding source over drugs used as controls. The pooled response rates of SSRIs, when associated with the funding source, are significantly greater than those of the same SSRIs when not associated with the sponsor (relative benefit=1.07; 95% confidence interval=1.02-1.11). The difference, however, is likely to be not of clinical importance.\n The effect of industry bias in comparative effectiveness reviews might play a lesser role than in systematic reviews of placebo-controlled trials.\n Copyright 2010 Elsevier Inc. All rights reserved.", "The serotonin reuptake inhibitors are the treatment of choice for patients with obsessive-compulsive disorder; however, empirical support for this assertion has been weaker for children and adolescents than for adults.\n To evaluate the safety and efficacy of the selective serotonin reuptake inhibitor sertraline hydrochloride in children and adolescents with obsessive-compulsive disorder.\n Randomized, double-blind, placebo-controlled trial.\n One hundred eighty-seven patients: 107 children aged 6 to 12 years and 80 adolescents aged 13 to 17 years randomized to receive either sertraline (53 children, 39 adolescents) or placebo (54 children, 41 adolescents).\n Twelve US academic and community clinics with experience conducting randomized controlled trials.\n Sertraline hydrochloride was titrated to a maximum of 200 mg/d during the first 4 weeks of double-blind therapy, after which patients continued to receive this dosage of medication for 8 more weeks. Control patients received placebo.\n The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH GOCS), and the NIMH Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) rating scales.\n In intent-to-treat analyses, patients treated with sertraline showed significantly greater improvement than did placebo-treated patients on the CY-BOCS (adjusted mean, -6.8vs -3.4, respectively; P=.005), the NIMH GOCS (-2.2 vs -1.3, respectively; P=.02), and the CGI-I (2.7 vs 3.3, respectively; P=.002) scales. Significant differences in efficacy between sertraline and placebo emerged at week 3 and persisted for the duration of the study. Based on CGI-I ratings at end point, 42% of patients receiving sertraline and 26% of patients receiving placebo were very much or much improved. Neither age nor sex predicted response to treatment. The incidence of insomnia, nausea, agitation, and tremor were significantly greater in patients receiving sertraline; 12 (13%) of 92 sertraline-treated patients and 3 (3.2%) of 95 placebo-treated patients discontinued prematurely because of adverse medical events (P=.02). No clinically meaningful abnormalities were apparent on vital sign determinations, laboratory findings, or electrocardiographic measurements.\n Sertraline appears to be a safe and effective short-term treatment for children and adolescents with obsessive-compulsive disorder." ]

[ "15084618", "18485252", "2679397", "12649101", "10703904", "10884634", "8829162", "11505416", "8630960" ]

[ "Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer.", "Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer.", "[Prevention of stomatitis induced by anti-cancer drugs].", "Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study.", "Efficacy of homeopathic treatment of skin reactions during radiotherapy for breast cancer: a randomised, double-blind clinical trial.", "Randomized clinical trial of the effectiveness of 3 commonly used mouthwashes to treat chemotherapy-induced mucositis.", "Randomized clinical trial of chlorhexidine versus placebo for prevention of oral mucositis in patients receiving chemotherapy.", "A randomized, controlled clinical trial of the homeopathic medication TRAUMEEL S in the treatment of chemotherapy-induced stomatitis in children undergoing stem cell transplantation.", "Prospective evaluation of a chamomile mouthwash for prevention of 5-FU-induced oral mucositis." ]

[ "The effectiveness of nonsteroid topical agents for the prevention of acute dermatitis during adjuvant radiotherapy for breast carcinoma has not been demonstrated. The goal of this study was to compare the effectiveness of calendula (Pommade au Calendula par Digestion; Boiron Ltd, Levallois-Perret, France) with that of trolamine (Biafine; Genmedix Ltd, France), which is considered in many institutions to be the reference topical agent.\n Between July 1999 and June 2001, 254 patients who had been operated on for breast cancer and who were to receive postoperative radiation therapy were randomly allocated to application of either trolamine (128 patients) or calendula (126 patients) on the irradiated fields after each session. The primary end point was the occurrence of acute dermatitis of grade 2 or higher. Prognostic factors, including treatment modalities and patient characteristics, were also investigated. Secondary end points were the occurrence of pain, the quantity of topical agent used, and patient satisfaction.\n The occurrence of acute dermatitis of grade 2 or higher was significantly lower (41% v 63%; P <.001) with the use of calendula than with trolamine. Moreover, patients receiving calendula had less frequent interruption of radiotherapy and significantly reduced radiation-induced pain. Calendula was considered to be more difficult to apply, but self-assessed satisfaction was greater. Body mass index and adjuvant chemotherapy before radiotherapy after lumpectomy were significant prognostic factors for acute dermatitis.\n Calendula is highly effective for the prevention of acute dermatitis of grade 2 or higher and should be proposed for patients undergoing postoperative irradiation for breast cancer.", "To evaluate the efficacy of pure natural honey as prophylaxis against radiochemotherapy-induced mucositis, through clinical scoring of oral and oropharyngeal mucositis, and culturing of pathogenic oral and oropharyngeal microbes.\n The study was done in Assiut University Hospital, Egypt, between January 2005 and July 2006. Forty patients diagnosed with head and neck cancer were entered into the trial. Enrolled patients were randomised to either the treatment group, receiving concomitant chemotherapy and radiotherapy (with a significant area of directly visible oral and/or oropharyngeal mucosa included in the radiation fields) plus prior topical application of pure natural honey, or the control group, receiving concomitant chemotherapy and radiotherapy without honey. Patients were evaluated clinically every week to assess development of radiation mucositis. Aerobic cultures and candida colonisation assessment were undertaken, via oral and oropharyngeal swabs, prior to and at the completion of irradiation, and when infection was evident.\n In the treatment group, no patients developed grade four mucositis and only three patients (15 per cent) developed grade three mucositis. In the control group, 13 patients (65 per cent) developed grade three or four mucositis (p < 0.05). Candida colonisation was found in 15 per cent of the treatment group and 60 per cent of the control group, either during or after radiotherapy (p = 0.003). Positive cultures for aerobic pathogenic bacteria were observed in 15 per cent of the treatment group and 65 per cent of the control group, during or after radiotherapy (p = 0.007).\n This study shows that prophylactic use of pure natural honey was effective in reducing mucositis resulting from radiochemotherapy in patients with head and neck cancer.", "A randomized control trial study was carried out to evaluate the effect of allopurinol mouth wash on stomatitis induced by chemotherapy in gynecologic patients. Chemotherapeutics used consisted of 5-FU+CDDP (PF) given to 10 patients and vincristine and actinomycin-D+cyclophosphamide (VAC) given to 5. Allopurinol mouth wash was prepared for patients to rinse their mouth with the solution 4-5 times daily before and after treatment with anti-cancer drugs. The Japan Society For Cancer Therapy's criteria for stomatitis were used. In the control group, stomatitis occurred in 9 of the 10 patients receiving PF therapy and in all of the 5 receiving VAC. In contrast, stomatitis was observed in only 2 of the 10 patients receiving PF therapy and 2 of the 5 VAC in the allopurinol-treated group. Allopurinol mouth wash showed a marked effect on stomatitis induced by chemotherapy.", "The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy.\n Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery.\n The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS).\n We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied.", "The aim of this study was to assess the effects of Belladonna 7cH and X-ray 15cH associated in the treatment of acute radiodermatitis. A randomized double-blind placebo-controlled clinical trial involving 66 patients who had been operated on for breast cancer and were undergoing radiotherapy was conducted. The following parameters were assessed over ten weeks: breast skin colour, warmth, swelling and pigmentation. The efficacy of the treatment was assessed by the comparison of these parameters taken individually and by calculating an Index of Total Severity (sum of the scores of the four parameters) during radiotherapy, and during recovery, 15 and 30 d after the end of the radiotherapy. The differences of the scores of the Index of Total Severity during Radiotherapy were not statistically significant, but showed a trend towards a better activity of the homoeopathic medicine compared to placebo. Analysis of the data on Total Severity during recovery, showed a statistically significant benefit of the active medicines over placebo. The homeopathic medicines had particular effectiveness on the heat of the skin. The limited number of patients observed and the posology employed could have interfered with the significance of the results. Chemotherapy and hormonotherapy do not seem to affect the results.", "To test the effectiveness of 3 mouthwashes used to treat chemotherapy-induced mucositis. The mouthwashes were as follows: salt and soda, chlorhexidine, and \"magic\" mouthwash (lidocaine, Benadryl, and Maalox). Study Design: A randomized, double-blind clinical trial was implemented in 23 outpatient and office settings. Participants were monitored from the time they developed mucositis until cessation of the signs and symptoms of mucositis, or until they finished their 12-day supply of mouthwash. All participants followed a prescribed oral hygiene program and were randomly assigned a mouthwash. Nurses used the Oral Assessment Guide for initial assessment and taught patients how to assess their own mouths, then phoned the patients every other day to gather status reports.\n In 142 of 200 patients, there was a cessation of the signs and symptoms of mucositis within 12 days. No significant differences in time for the cessation of the signs and symptoms were observed among the 3 groups.\n Given the comparable effectiveness of the mouthwashes, the least costly was salt and soda mouthwash.", "To test the effectiveness of a nurse-initiated systematic oral hygiene teaching program-PRO-SELF: Mouth Aware (PSMA)-in conjunction with two mouthwashes (0.12% chlorhexidine or sterile water) in preventing chemotherapy-induced oral mucositis.\n Randomized, double-blind, placebo-controlled, clinical trial.\n 23 outpatient clinics and office practices in California.\n 222 patients who were starting a cycle of mucositis-inducing chemotherapy.\n Participants were followed over three chemotherapy cycles. All patients were provided the PSMA program. Random assignment to a mouthwash occurred prior to the development of oral mucositis. Researchers used the Oral Assessment Guide to assess the patients oral cavities monthly (with the patients cycles of chemotherapy) and when patients reported any oral changes between cycles.\n Type of mouthwash, incidence, days to onset, and severity of chemotherapy-induced oral mucositis.\n No significant differences existed between the two mouthwashes in regard to incidence, days to onset, and severity of mucositis.\n Because chlorhexidine (S20 per pint) was no more effective than water, a substantial cost savings can be realized by rinsing with water. Interestingly, the PSMA program appeared to reduce the incidence of mucositis from on a prior estimate of 44% to less than 26%.\n A nursing prescription of a systematic oral hygiene program using water as a mouth rinse is cost efficient and may be effective in preventing oral mucositis.", "Stomatitis is a common consequence of chemotherapy and a condition for which there is little effective treatment. Although the management of patients with other chemotherapy-related toxicities has improved in recent years, the incidence of stomatitis is increasing because of more intensive treatment and is often a dose limiting factor in chemotherapy. The authors assessed the efficacy of a homeopathic remedy, TRAUMEEL S(R), in the management of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation.\n A randomized, placebo-controlled, double-blind clinical trial was conducted in 32 patients ages 3-25 years who had undergone allogeneic (16 patients) or autologous (16 patients) stem cell transplantation. Of the 30 evaluable patients, 15 were assigned placebo, and 15 were assigned TRAUMEEL S both as a mouth rinse, administered five times daily from 2 days after transplantation for a minimum of 14 days, or until at least 2 days after all signs of stomatitis were absent. Stomatitis scores were evaluated according to the World Health Organization grading system for mucositis.\n A total of five patients (33%) in the TRAUMEEL S treatment group did not develop stomatitis compared with only one patient (7%) in the placebo group. Stomatitis worsened in only 7 patients (47%) in the TRAUMEEL S treatment group compared with 14 patients (93%) in the placebo group. The mean area under the curve stomatitis scores were 10.4 in the TRAUMEEL S treatment group and 24.3 in the placebo group. This difference was statistically significant (P < 0.01).\n This study indicates that TRAUMEEL S may reduce significantly the severity and duration of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation.\n Copyright 2001 American Cancer Society.", "Stomatitis has been found to be a major dose-limiting toxicity from bolus 5-fluorouracil-based (5-FU) chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data which suggested that a chamomile mouthwash might ameliorate this toxicity, a prospective trial was developed to test chamomile in this situation.\n A Phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered into the study at the time of their first cycle of 5-FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5-FU. In addition, each patient was randomized to receive a chamomile or placebo mouthwash thrice daily for 14 days. Stomatitis scores were determined by health care providers and by patients themselves.\n There were 164 evaluable and well-stratified patients equally randomized to both treatment groups. There was no suggestion of any stomatitis difference between patients randomized to either protocol arm. There was also no suggestion of toxicity. Subset analysis did reveal unsuspected differential effects between males and females that could not be explained by reasons other than chance.\n The resultant data from this clinical trial did not support the prestudy hypothesis that chamomile could decrease 5-FU-induced stomatitis." ]

[ "12074203", "1520054", "2669346", "59150", "9048790", "15808033", "2051002", "2043179", "1457907" ]

[ "Effectiveness of quinine in treating muscle cramps: a double-blind, placebo-controlled, parallel-group, multicentre trial.", "Treatment of nocturnal leg cramps. A crossover trial of quinine vs vitamin E.", "Placebo-controlled trial of quinine therapy for nocturnal leg cramps.", "Prevention of muscle cramps in haemodialysis patients by quinine sulphate.", "Randomised controlled trial of hydroquinine in muscle cramps.", "Managing nocturnal leg cramps--calf-stretching exercises and cessation of quinine treatment: a factorial randomised controlled trial.", "A randomized controlled trial of quinidine in the treatment of cirrhotic patients with muscle cramps.", "[Treatment of nocturnal leg cramps. A multicenter, double blind, placebo controlled comparison between the combination of quinine and theophylline ethylene diamine with quinine].", "Dialysis leg cramps. Efficacy of quinine versus vitamin E." ]

[ "To determine the efficacy and safety of quinine in treating nocturnal muscle cramps we performed a double-blind, placebo-controlled, parallel-group, multicentre trial in 17 general practice centres in Germany. Ninety-eight patients aged 18-70 years with more than six muscle cramps in two weeks were enrolled. A two-week run-in period without treatment was followed by two weeks of treatment with 400 mg quinine or placebo per day and a wash-out period of two weeks without treatment. The primary outcome measure was the reduction in the number of muscle cramps between the run-in and treatment periods. The intensity of cramps, number of nights with cramps, sleep disturbance and intensity of pain were recorded as secondary outcome measures. At baseline the median number of cramps was 12 in two weeks in both groups. The median reduction between the run-in and therapy phases was eight (95% CI 7-10) versus six (95% CI 3-7) muscle cramps during quinine and placebo treatment; 36 (80%) participants in the quinine group and 26 (53%) in the placebo group had a reduction of at least 50% in the number of muscle cramps. Frequency, intensity and pain at night showed a statistically significant difference in favour of quinine. The improvement was more evident according to physician assessment than patient assessment; this is corroborated by the high placebo response rate. No significant differences were found between the two groups with respect to side-effects. Short term treatment with 400 mg quinine per day can effectively prevent nocturnal leg cramps in adults without relevant side-effects.", "This study compared the efficacy and safety of quinine sulfate, vitamin E, and placebo in the treatment of nocturnal leg cramps.\n A random-order, double-blind, placebo-controlled crossover trial was performed.\n The study was conducted at the Veterans Affairs Medical Center, White River Junction, Vt.\n Twenty-seven male veterans, aged 38 to 73 years, who experienced at least six leg cramps per month were recruited through the general medicine walk-in clinic or were referred from other clinics. Fifty-five subjects were contacted, 30 were enrolled consecutively, and 27 completed the study.\n Subjects received, in random order, quinine sulfate (200 mg at supper and 300 mg at bedtime), vitamin E (800 U at bedtime), or placebo for 4-week periods. These periods were separated by 4-week washout intervals.\n Patients reported cramp frequency, severity, and sleep disturbance caused by cramps.\n Compared with treatment with placebo, quinine reduced the frequency of cramps and sleep disturbance, but not the average cramp severity. Thirteen of 27 patients had at least a 50% reduction in the number of cramps while receiving quinine; the response was usually seen within 3 days. There was evidence of a mild increase in side effects while subjects received quinine. Vitamin E was not effective in reducing leg cramp frequency, severity, or sleep disturbance.\n Quinine sulfate, but not vitamin E, is superior to placebo in the treatment of nocturnal leg cramps.", "A prospective, double-blind, placebo-controlled crossover study of the use of quinine for nocturnal leg cramps was carried out in 8 elderly volunteer patients. The patients were randomly assigned to receive either placebo or 200 mg of quinine sulfate by mouth at bedtime. After 4 weeks of treatment and after a one-week washout period, the group taking quinine switched to placebo and vice versa for another 4 weeks. The differences in the number, duration, and severity of cramps and the side effects were compared. All of the patients had fewer cramps and decreased severity and duration of attacks while receiving quinine. Mild side effects developed in only 2 patients, and these subsided without treatment or discontinuing the medication. We conclude that quinine was effective in relieving nocturnal leg cramps in a selected group of elderly patients.", "Nine patients on maintenance haemodialysis with frequent muscle cramps were given 320 mg quinine sulphate or placebo (in an identical gelatin capsule) at the beginning of each dialysis for a period of 12 weeks. The frequency of cramps was significantly reduced during dialysis in patients receiving quinine sulphate. None of the haematological, auditory, or visual disturbances ascribed to quinine sulphate were noted.", "Although quinine and hydroquinine are commonly prescribed for muscle cramps, controlled clinical trials of these drugs have reported mixed findings about efficacy. We investigated hydroquinine therapy in otherwise healthy adults who had frequent, ordinary muscle cramps.\n This randomised, double-blind, placebo-controlled, parallel-group trial consisted of three consecutive 2-week periods: qualification, treatment, and washout, 68 women and 44 men who had at least three muscle cramps per week were enrolled. During the treatment period, participants were randomly assigned 300 mg daily dose of hydroquinine hydrobromide dihydrate (54 participants) or placebo (58). The frequency, severity (1-10), duration, and location of muscle cramps, as well as any side-effects, were recorded by participant in daily diaries. The primary outcome measures were the number of muscle cramps and the number of days during which the participants had muscle cramps (cramp-days).\n We excluded five participants from both groups from the analysis. Thus, data from 49 hydroquinine-group participants and 53 placebo-group participants were analysed. In both groups the total number of muscle cramps and the number of cramp-days decreased during the treatment period compared with the qualification period. However, these improvements were greater in the hydroquinine group than in the placebo group. The hydroquinine-group participants reported a median of 8 (95% CI 7-12) fewer cramps and median of 3 (1-4) fewer cramp-days, whereas those on placebo reported only 3 (0-5) fewer cramps and 1 (0-5) fewer cramp-days. 32 (65%) of participants in the hydroquinine group had a 50% or greater reduction in the number of muscle cramps. After the onset of cramps, hydroquinine did not reduce the severity or duration of cramps. We also found a sustained effect after treatment had stopped. Hydroquinine was well tolerated, and resulted in only mild side-effects.\n In our study, 300 mg hydroquinine was safe to take in the short-term and significantly more effective than placebo in the prevention of frequent, ordinary muscle cramps. This therapeutic effect outlasted the duration of treatment.", "Quinine is a common treatment for nocturnal leg cramps but has potential side effects. An uncontrolled study suggested that calf-stretching exercises could prevent nocturnal leg cramps (night cramps) but these findings have never been confirmed.\n To assess the effect of calf-stretching exercises and cessation of quinine treatment for patients with night cramps taking quinine.\n Randomised controlled trial.\n Twenty-eight general practices in southern England.\n One hundred and ninety-one patients prescribed quinine for night cramps were randomised to one of four groups defined by two \"advice\" factors: undertake exercises and stop quinine. After 6 weeks they were advised that they could take quinine and undertake the exercises freely. Documentation of cramp at 12 weeks was achieved in 181 (95%) patients. Main outcome measures were: symptom burden score, and frequency of night cramps and quinine usage.\n At 12 weeks there was no significant difference in number of cramps in the previous 4 weeks (exercise = 1.95, 95% confidence interval [CI] = -3.01 to 6.90; quinine cessation = 3.45, 95% CI = -1.52 to 8.41) nor symptom burden or severity of cramps. However, after 12 weeks 26.5% (95% CI = 13.3% to 39.7%) more patients who had been advised to stop quinine treatment reported taking no quinine tablets in the previous week (odds ratio [OR] = 3.32, 95% CI = 1.37 to 8.06), whereas advice to do stretching exercises had no effect (OR = 0.73, 95% CI = 0.27 to 1.98).\n Calf-stretching exercises are not effective in reducing the frequency or severity of night cramps. Advising those on long-term repeat prescriptions to try stopping quinine temporarily will result in no major problems for patients, and allow a significant number to stop medication.", "In an attempt to evaluate the effect of quinidine in the treatment of patients with cirrhosis and muscle cramps, 31 cirrhotic patients with muscle cramps were randomly divided into two groups and given orally 400 mg of quinidine sulfate per day or placebo, respectively. Baseline clinical and laboratory data for these two groups were similar. Four weeks after oral administration of quinidine, the number of cramps significantly decreased from 14.4 +/- 1.7 (mean +/- S.E.) to 4.4 +/- 1.1 episodes (p less than 0.0001), but it remained unchanged in the placebo group (from 11.8 +/- 1.0 to 11.5 +/- 1.5 episodes, p greater than 0.05). In addition, 88% of the 16 patients on quinidine and 13% of the 15 patients on a placebo showed a greater than 50% reduction in the number of cramps during a 4-week treatment period (p less than 0.0001). The peak and trough serum levels of quinidine in patients having received quinidine for 2 weeks were 1.3 +/- 0.1 and 0.7 +/- 0.1 mg/l, respectively. There was a significant relationship between serum quinidine concentrations and attenuation of cramps. No significant adverse effect was observed during the study, except for five (31%) patients who developed mild diarrhea after quinidine therapy. Diarrhea subsided spontaneously or was controlled by medications without the interruption of quinidine therapy. It was concluded that quinidine is a safe and effective drug for the treatment of cirrhotic patients with muscle cramps.", "164 patients (m = 45, w = 119; age 55.7 +/- 14.7 years) took part in a multicentric controlled parallel-double blind study in which efficacy and tolerability of the combination quinine sulfate (CAS 6119-70-6) plus theophylline ethylene diamine (CTED, CAS 317-34-0) (Limptar) in the treatment of the recurrent nocturnal leg cramps were investigated. Only patients who suffered before the begin of the study in at least three nights per week from leg cramps were included. The duration of the study was three weeks. In the first week all patients were treated in a single blind design with placebo. The subsequent 2 weeks were carried out double-blind. The global efficacy judged by the physicians and investigated for the 126 patients who took the compounds at least four days within the random phase was remarkably better for the combination than for quinine or placebo (very good and good in 87.1 vs. 63.7 vs. 39.5% of the cases; p less than 0.001; x-test). In 117 patients an analysis of the time course of the efficacy could be done from the notes in the diary (minimum duration of treatment 11 d). Already within the first week there was a highly significant decrease of nights with leg cramps within the CTED group (n = 34) from 4.68 (95% confidential interval 2.26-7.0) to 2.25 (0-6.78) in comparison to placebo (n = 40; from 4.32 [1.9-7.0] to 3.69 [1.22-6.91]) and quinine (n = 43; from 4.78 [2.22-7.0] to 3.27 [0-7.0]; F-test; p = 0.0001 resp. 0.0012).(ABSTRACT TRUNCATED AT 250 WORDS)", "A controlled randomized double-blind study was done to determine the frequency and severity of leg cramps in 40 patients on dialysis with a history of leg cramps. All patients entered a 2 month placebo washout and were randomized into a 2 month double-dummy phase of quinine 325 mg at bedtime versus vitamin E 400 IU at bedtime. Of the 29 patients completing the study, 16 received quinine and 13 vitamin E. During placebo washout, the vitamin E group had a mean of 10.4 leg cramps per month, and the quinine group had a mean of 10.9. The vitamin E and quinine groups had a 1 month reduction in leg cramps to 3.3 and 3.6, respectively (p < 0.0005 for both groups combined); this was sustained at 2 months. A severity of pain index showed a statistically significant decrease for both groups. The 95% confidence interval for the difference between the number of leg cramps after vitamin E versus quinine treatment (95% confidence interval, -3.8, +3.2) suggests similar efficacy. Quinine and vitamin E were effective treatments for leg cramps in these patients. Considering the potential toxicity of quinine, vitamin E is recommended as the initial treatment of choice for patients on dialysis with leg cramps." ]

[ "16801465", "12137603", "17975231", "8167383", "10082500", "17591533", "15923569", "11431176", "14990637" ]

[ "Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial.", "[The effects of angiotensin-converting enzyme inhibitor on IgA nephropathy and the influencing factors].", "N-acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre-existing moderate renal insufficiency.", "ACE inhibitor mediated reductions in renal size and microalbuminuria in normotensive, diabetic subjects.", "ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients.", "ACE inhibitors and persistent left ventricular hypertrophy after renal transplantation: a randomized clinical trial.", "Successful implementation of the randomized discontinuation trial design: an application to the study of the putative antiangiogenic agent carboxyaminoimidazole in renal cell carcinoma--CALGB 69901.", "Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy.", "Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines." ]

[ "Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function.\n We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13).\n Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.", "OBJECTIVE To investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) on IgA nephropathy(IgAN) and the factors influencing the therapeutic effects. METHODS 131 cases with IgAN diagnosed by renal biopsy were randomly divided into two groups: ACEI group (benazepril 10 mg/d) and non-ACEI group as control. The pathological changes in the kidney were analyzed using Lee SMK. RESULTS After 1 month treatment of ACEI, the levels of proteinuria and serum cholesterol decreased significantly, meanwhile those of serum albumin and total protein increased obviously in patients with IgAN(P < 0.05). The proteinuria level at the 3rd month after treatment was lower than that at the 1st month, but was same as that at the 18th month. While in the control group the proteinuria level increased and the clearance of creatinine decreased continuously during the observation (P < 0.05). The effects correlated positively with mesangial proliferation and negatively with course of the disease glomerular sclerosis in glomerulus and changes of small arterioles in the kidney. Normal blood pressare normal renal function I approximately II degree of Lee SMK I degee of interstitial changes minimal changes of small arterioles and mild glomerular sclerosis predicted better response to ACEI treatment than hypertension renal insufficiency V degree of Lee SMK IV degee of interstitial changes severe changes of small arterioles and massive glomerular sclerosis. CONCLUSIONS It is suggested that benezepril could definitely reduce the excretion of urinary protein and protect renal function of patients with IgAN and should be used as earlier as possible. Mesangial prolife ration glomerular sclerosis in glomerulus changes of small arterioles in kidney and course of the disease are the major influencing factors of ACEI treatment on IgAN.", "N-acetylcysteine may prevent acute kidney injury after cardiac surgery. To determine if N-acetylcysteine warrants definitive evaluation in a large multicentre trial, we evaluated its effects on a surrogate outcome, estimated glomerular filtration rate (eGFR), in a randomized trial.\n One-hundred-seventy-seven cardiac surgery patients with moderate pre-existing renal insufficiency (eGFR <or= 60 mLxmin(-1)) were recruited in a blinded (patients, clinicians, data-collectors) placebo-controlled randomized trial. Eighty-nine were randomized to N-acetylcysteine (100 mgxkg(-1) i.v. bolus, 20 mgxkg(-1)xhr(-1) infusion until four hours after cardiopulmonary bypass), and 88 to placebo. The primary outcome was the percent change in eGFR during the first 72 postoperative hours. Secondary outcomes included renal replacement therapy, mortality, atrial fibrillation, vasoactive medications, and adverse effects. A future multicentre trial was deemed to be warranted if N-acetylcysteine was associated with a percent change in eGFR that was 3.8 better (small benefit), and with an upper 95% confidence interval including 9.5 (moderate benefit).\n The median percent change in eGFR was 5.2% better (absolute difference) in the N-acetylcysteine arm (95% confidence interval 2.4% worse to 12.1% better; P=0.22). With regard to secondary outcomes, all-cause mortality was lower in the N-acetylcysteine arm (0% vs 8%; P=0.007).\n N-acetylcysteine did not cause a statistically significant improvement in postoperative eGFR in this single-centre study. Nonetheless, its treatment effect was consistent with a plausible small-to-moderate benefit. Given this finding, N-acetylcysteine should be definitively evaluated in a large randomized trial.", "Recent studies utilizing converting enzyme inhibitors (CEI) in diabetic rats document reductions in both renal hypertrophy and albuminuria. Four separate clinical studies in normotensive patients with diabetes demonstrate reduction of microalbuminuria with CEIs independent of blood pressure reduction. The present pilot study examines the results of reducing an elevated glomerular filtration rate on changes in renal size and microalbuminuria in normotensive, hyperfiltering insulin-dependent diabetic (IDDM) patients. Fifteen IDDM patients were randomized to either placebo or the CEI, lisinopril. Dosage of lisinopril was titrated over 3 months to reduce glomerular filtration rate (GFR) to < or = 2.33 mL/sec. Evaluation at 18 months demonstrated the lisinopril group had a marked reduction in renal size (16.9 +/- 1.1, baseline versus 12.8 +/- 0.9 cm, 18 months; p < 0.05) and microalbuminuria (92 +/- 11 micrograms/min, baseline versus 23 +/- 26 micrograms/min, 18 months; p < 0.05). No change in renal size was noted in the placebo group (15.4 +/- 0.8, baseline versus 14.9 +/- 0.7 cm, 18 months; NS) and albuminuria increased (118 +/- 15 micrograms/min, baseline versus 293 +/- 32 micrograms/min, 18 months; p < 0.05). Mean arterial pressure at 18 months was significantly lower in the lisinopril group compared to placebo (102 +/- 4, placebo versus 87 +/- 6 mm Hg, CEI, p < 0.05). This study supports previous animal studies that document reductions in both microalbuminuria and renal size by a CEI. The overall impact of these findings on preservation of renal function cannot be assessed, however, in this short-term study.", "Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the beta-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after 24 months in the atenolol group; P=NS for both groups). After 24 months, the change in urinary albumin excretion from baseline was -10+/-15 mg/d in the quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function.", "Interventional studies of left ventricular hypertrophy (LVH) in renal transplant recipients are scarce and to date evaluated only patients immediately after renal transplantation.\n Randomized controlled trial that assessed the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in regressing persistent LVH after successful transplantation.\n 70 renal transplant recipients (47 men; age, 30 to 68 years) without diabetes previously randomly assigned to either cyclosporine or tacrolimus therapy, with LVH persisting 3 to 6 months after transplantation.\n Subjects were randomly assigned to either lisinopril (ACE-inhibitor group; 36 patients) or no therapy (control group; 34 subjects).\n Main outcome was change in left ventricular mass index (LVMi) at month 18.\n A consistent decrease in both systolic (SBP) and diastolic blood pressure (DBP) was observed in both groups (between-group differences, -1.7 +/- 3.3 mm Hg; 95% confidence interval [CI], -4.8 to 8.2; P = 0.6 for SBP; 0.3 +/- 2.2 mm Hg; 95% CI, -4.8 to 4.1; P = 0.9 for DBP), whereas LVMi regressed more in the ACE-inhibitor group (between-group difference, 10.1 +/- 16.3 g/m(2.7); 95% CI, 4.2 to 16.1; P < 0.01). A significant interaction of ACE inhibitors with cyclosporine in affecting LVMi change was shown by means of post hoc multiple regression analysis (P < 0.01; differences between cyclosporine and tacrolimus group, 13.3 +/- 3.9 g/m(2.7); 95% CI, 5.3 to 21.2; P < 0.01 in the ACE-inhibitor group; 3.7 +/- 4.2 g/m(2.7); 95% CI, -4.7 to 12.2; P = 0.4 in the control group).\n Single-center study with small sample size. Interaction of ACE inhibitors with cyclosporine treatment emerged from post hoc analysis.\n A prolonged course of ACE-inhibitor therapy is effective in regressing the persistent LVH of renal transplant recipients by mechanisms independent of effects on BP. This regression seems to be at least in part the effect of an interaction between ACE inhibitors and cyclosporine.", "To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design.\n Recruited patients had a performance status of 0 to 2, minimal neuropathy or cerebellar dysfunction, measurable disease, and normal organ function. Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response. Protocol treatment was discontinued for unacceptable toxicity or progressive disease; patients with stable disease at the 16-week evaluation point were randomly assigned in a double-blind manner to continued CAI or placebo. The primary end point was the stable disease rate in the randomized groups.\n A total of 368 patients were accrued and received therapy. Ninety percent had a performance status of 0 or 1, 80% underwent a prior nephrectomy, and 41% had received no prior systemic therapy. Serious or life-threatening toxicity was experienced by 34%, with asthenia (15%) and neuropsychiatric difficulties (7%) being most common. At the randomization point, 51% of patients had progressed, 30% withdrew, 1% experienced a partial response, and 17% had stable disease and were randomly assigned. A Bayesian futility analysis utilizing the first 49 randomly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9% even under the most optimistic a priori assumptions, and further trial accrual was halted.\n CAI is inactive in RCC. The RDT design should be further explored for evaluating activity of putative disease stabilizing agents.", "Angiotensin-converting enzyme (ACE) inhibitors and AT1-receptor antagonists (ARAs) are widely administered to reduce urinary protein loss and slow the progression of proteinuric nephropathy to end-stage renal failure. Our group recently observed that the combination of ACE inhibitors and ARAs may have an additive antiproteinuric effect, which may occur because ACE inhibitors do not completely reduce angiotensin II (Ang II) production. Ang II is also produced by chymase. Thus, combination therapy better antagonizes the effects of Ang II. The purpose of this study is to ascertain whether the additive antiproteinuric effect of ACE inhibitors plus ARAs is dose dependent and related to the drug-induced reduction in systemic blood pressure. Therefore, enalapril (E; 10 mg/d) and losartan (LOS; 50 mg/d) were randomly administered alone and then in association; initial dosages were doubled when drugs were administered alone and in association. To determine the influence of the drug-dependent effect on reducing blood pressure and the reduction in urinary proteinuria, both ambulatory and office blood pressures were recorded. E and LOS administered alone reduced proteinuria by the same extent; no further reduction was observed when E and LOS alone were administered at a doubled dose. When E and LOS were coadministered, proteinuria decreased by a greater extent compared with E and LOS alone; an additional reduction in proteinuria was observed when combined therapy doses were doubled. The reduction in proteinuria was not correlated with clinical through blood pressure; however, reductions in diastolic and mean ambulatory blood pressures significantly correlated with the decrease in proteinuria, as well as with creatinine clearance. In conclusion, this study shows that combination therapy with E and LOS has an additive dose-dependent antiproteinuric effect that is likely induced by the drug-related reduction in systemic blood pressure. In normotensive proteinuric patients, it is likely that even a small reduction in systemic blood pressure may affect intraglomerular hemodynamics by a great extent because efferent arteriole regulation is hampered more completely by the coadministration of ACE inhibitors and ARAs.", "To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer.\n This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure.\n There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m(2); P =.55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (-8.59 v 1.85 g/cm(2); P =.033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P =.11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P =.0003) and fatigue (10% v 0%; P =.013).\n Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions." ]

[ "15364042", "14643092", "1821833", "9137848", "18077797", "9415509", "8937535", "15061241", "17938371" ]

[ "Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia.", "Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial.", "Neuropsychological assessment in lamotrigine treated epileptic patients.", "Lamotrigine versus placebo in the prophylaxis of migraine with and without aura.", "Adjunctive lamotrigine for partial seizures in patients aged 1 to 24 months.", "Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial.", "Controlled trial of lamotrigine (Lamictal) for treatment-resistant partial seizures.", "Conjugated estrogens as adjuvant therapy in the treatment of acute schizophrenia: a double-blind study.", "Lamotrigine extended-release as adjunctive therapy for partial seizures." ]

[ "Lamotrigine, a novel anticonvulsant drug having modulatory effects on glutamatergic neurotransmission, improves mood and cognition parameters in bipolar disorder. Recent studies suggest that when added to clozapine, lamotrigine treatment may result in significant positive symptoms reductions in schizophrenia. Similar effects were not observed in an open trial in which lamotrigine was used as adjuvant to nonclozapine antipsychotics.\n Thirty-eight treatment-resistant schizophrenia inpatients receiving conventional and atypical antipsychotics enrolled in a 10-week, double-blind, placebo-controlled study, in which they were randomized in a 2:1 ratio to receive adjuvant treatment with lamotrigine, gradually titrated to a 400 mg/day dose, or placebo. Of these, 31 completed the trial. Measures of clinical efficacy and side effects were determined every other week. Serum levels of amino acids were assessed at the beginning and end of the study.\n In primary last observation carried forward analysis, no statistically significant between-group differences were observed; however, the completers' analyses revealed that lamotrigine treatment resulted in significant (p < or = .05) reductions in positive and general psychopathology symptoms, as measured by the Positive and Negative Syndrome Scale. No significant differences in lamotrigine effects were noted between conventional versus atypical antipsychotics. Lamotrigine treatment was well tolerated, and glutamate serum levels remained stable throughout the study.\n These preliminary findings 1) support the hypothesis that lamotrigine adjuvant treatment may improve positive symptoms and general psychopathology in schizophrenia, 2) suggest that beneficial effects may be achieved when lamotrigine is added to both conventional and atypical antipsychotics, and 3) warrant additional, larger scale trials.", "There is no evidence from randomized, controlled trials that demonstrate effectiveness for any pharmacological treatment in clozapine-resistant schizophrenia. Since the introduction of chlorpromazine, all antipsychotics with proven efficacy on positive symptoms have been dopamine antagonists, but recent experimental data suggest that ketamine-induced positive schizophreniform symptoms in healthy subjects can be controlled by a glutamate antagonist lamotrigine. The hypothesis tested was that lamotrigine is more effective than placebo in the treatment of positive schizophrenic symptoms when combined with clozapine.\n Thirty-four hospitalized treatment-resistant patients having chronic schizophrenia participated in a double-blind, placebo-controlled, 14-week, crossover trial where 200 mg/day lamotrigine was gradually added to their ongoing clozapine treatment. Clinical assessments were made by the Positive and Negative Syndrome Scale at the beginning and end of each treatment period.\n In intention-to-treat analysis, lamotrigine treatment was more effective in reducing positive (effect size.7, p =.009) and general psychopathological (effect size.6, p =.030) symptoms, whereas no improvement was observed in negative symptoms.\n These results provide the first evidence from a randomized controlled trial of an effective pharmacological treatment with an anticonvulsant agent in treatment-resistant schizophrenia and indicate that both positive and general psychopathological symptoms in patients with schizophrenia can be controlled by a drug that is not a dopamine antagonist. The results are in line with previous experimental data suggesting that excessive glutamate neurotransmission contributes to the positive symptoms of schizophrenia.", "A double-blind, placebo controlled cross over study assessed the efficacy of lamotrigine as adjunct therapy for patients with refractory partial seizures. In addition to the main study, a neuropsychological component evaluated three main areas of cognitive function. These included: i) Concentration and attention; ii) General Cerebral Efficiency, and iii) Mnestic functions--immediate, short term and new learning ability. Ten subjects (4 males, 6 females, age range 22 to 53, mean age 31.3 years) were involved in the study, each assessed 3 times--baseline, end of phase I and end of phase II. Whilst statistical analysis proved impracticable due to differing scores across cells, between the results of lamotrigine and placebo, clinically, there appeared to be a marginal reduction in General Cerebral Efficiency during the lamotrigine phase. In the light of these tests, the conclusion is advanced that lamotrigine does not specifically impair cognitive function, and that it does not impair mnestic function. An alternate hypothesis of interaction effects is posited for the slight reduction in speed of information processing.", "Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of glutamate. Release of glutamate may be essential in the propagation of spreading cortical depression, which some believe is central to the genesis of migraine attacks. This study compared safety and efficacy of lamotrigine and placebo in migraine prophylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo-responders and non-compliers were excluded, leaving 77 to be treated with lamotrigine (n = 37) or placebo (n = 40) for up to 3 months. Initially, lamotrigine therapy was commenced at the full dose of 200 mg/day, but, following a high incidence of skin rashes, a slow dose-escalation was introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on lamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that lamotrigine is ineffective for migraine prophylaxis. There were more adverse events on lamotrigine than on placebo, most commonly rash. With slow dose-escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups.", "This randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy and tolerability of adjunctive lamotrigine for the treatment of partial seizures in infants aged 1 to 24 months.\n The study used a responder-enriched design in which all patients received adjunctive lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1 mg/kg/day for those on non-enzyme-inducing antiepileptic drugs [AEDs] or valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting response criteria were randomly assigned to double-blind treatment for up to 8 weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine (placebo; n = 19) while background AEDs were maintained.\n The proportion of treatment failures (patients who met escape criteria or withdrew before completing the double-blind phase) was lower with lamotrigine (58%) than with placebo (84%). This finding was not significant in the primary analysis (two-sided chi(2) test [primary endpoint]). A post hoc sensitivity analysis of the primary endpoint was also performed (p = 0.045 by one-sided, mid-p corrected Fisher exact test). The median time to meet escape criteria was longer with lamotrigine (42 days) than with placebo (22 days) (p = 0.059). During the last 28 days of the open-label phase, 53% of the patients had a >or=50% reduction in frequency of partial seizures with lamotrigine. Additional reduction in partial seizure frequency was observed during the double-blind phase compared with the last 4 weeks of the open-label phase among those randomly assigned to lamotrigine (32% with a >or=25% reduction) but not those randomly assigned to placebo (5% with a >or=25% reduction). Lamotrigine was well tolerated, with an adverse event profile comparable to that observed in older pediatric patients.\n Lamotrigine was well tolerated, and the data indicate that it may be efficacious in the treatment of partial seizures in infants aged 1 to 24 months.", "Lamotrigine is a chemically novel antiepileptic drug which has not been adequately assessed for its antineuralgic properties. It was used in a double-blind placebo controlled crossover trial in 14 patients with refractory trigeminal neuralgia. Patients continued to take a steady dose of carbamazepine or phenytoin throughout the trial over a 31-day period. Each arm of the trial lasted 2 weeks with an intervening 3-day washout period. The maintenance dose of lamotrigine was 400 mg. Lamotrigine was superior to placebo (P = 0.011) based on analysis of a composite efficacy index which compared the numbers of patients assigned greater efficacy on lamotrigine with those assigned greater efficacy on placebo. Efficacy for one treatment over another was determined according to a hierarchy of: (i) use of escape medication; (ii) total pain scores; or (iii) global evaluations. Eleven of the 13 patients eligible for inclusion in the composite efficacy index showed better efficacy on lamotrigine compared with placebo. Global evaluations further suggested that patients did better on lamotrigine than placebo (P = 0.025). The adverse reactions with both lamotrigine and placebo were predominantly dose-dependent effects on the central nervous system. A 14th patient withdrew from the study due to severe pain during the placebo arm of the trial. It would appear that lamotrigine has antineuralgic properties.", "The antiepileptic effect of lamotrigine (Lamictal) was assessed in a double-blind, placebo-controlled, crossover trial in 56 adult patients with refractory partial seizures. Lamotrigine or placebo was added to the patients' existing antiepileptic drugs (AEDs). The dose of lamotrigine varied from 75 to 400 mg daily. Thirty-eight patients completed the trial and 7 withdrew because of adverse experiences. There was a statistically significant reduction in seizure counts on lamotrigine compared with placebo for total seizures (30.3% reduction, 95% CI 8.4%, 47.0%), complex partial seizures (29.2% reduction, 95% CI 3.8%, 47.9%) and secondary generalised seizures (37.9%, CI 18.9%, 52.4%). The analysis of total seizure days showed a similar significant reduction during lamotrigine treatment for the same seizure categories. There was no statistically significant difference in reporting of adverse events between lamotrigine and placebo except for dizziness which was reported more frequently on lamotrigine than on placebo. There were no differences in abnormal haematological or biochemical findings between lamotrigine and placebo, and lamotrigine had no effect on plasma concentrations of concomitant AEDs.", "In a double-blind, placebo controlled study, conjugated estrogens (CE) (0.625 mg/day) were added to a fixed dosage of haloperidol (5 mg daily). Forty-four female inpatients with acute schizophrenia were included in the study and randomized to one of the groups; 40 patients completed the trial. They were followed for 28 days and evaluated periodically with the BPRS, Negative Symptoms Rating Scale, Simpson Angus Extrapyramidal Rating Scale and UKU rating scale. Hormonal concentrations (estradiol, estrone, progesterone, FSH, LH and prolactine) were measured at baseline and weekly throughout the trial. Both groups showed similar clinical improvement during the evaluation, although there was a trend for the CE group to show a better improvement than the placebo group (p < 0.10). Side effects and the use of anticholinergics were similar in both groups. Conjugated estrogens caused elevation only of estrone levels in the CE group; estradiol and prolactin showed a similar profile for both groups. Our negative findings regarding the antipsychotic effect of conjugated estrogens does not preclude, however, a possible efficacy of other estrogens, such as 17-beta-estradiol, in schizophrenia.", "To evaluate the efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for partial seizures in epilepsy.\n Patients more than 12 years old diagnosed with epilepsy with partial seizures and taking one to two baseline antiepileptic drugs were randomized to adjunctive once-daily lamotrigine XR or placebo in a double-blind, parallel-group trial. The study comprised a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase during which doses of study medication and concomitant antiepileptic drugs were maintained.\n Of the 243 randomized patients, 239 (118 lamotrigine XR, 121 placebo) entered the escalation phase and received study medication. Lamotrigine XR was more effective than placebo with respect to median percent reduction from baseline in weekly partial seizure frequency (primary endpoint-entire 19-week treatment phase: 46.6% vs 24.5%, p = 0.0001 [corrected] via Wilcoxon test; escalation phase: 29.8% vs 15.6%, p = 0.027; maintenance phase: 58.4% vs 26.8%, p [corrected] < 0.0001). The percentage of patients with >or=50% reduction in partial seizure frequency (44.0% vs 20.8%, p = 0.0002) [corrected] and time to >or=50% reduction in partial seizure frequency (p = 0.0001) [corrected] also favored lamotrigine XR over placebo. A similar pattern of results was observed for secondarily generalized seizures. The most common adverse events were headache (lamotrigine XR 16%, placebo 18%) [corrected] and dizziness (lamotrigine XR 19%, [corrected] placebo 5%). Differences between lamotrigine XR and placebo on health outcomes measures were not significant.\n Once-daily adjunctive lamotrigine extended-release compared with placebo effectively reduced partial seizure frequency and was well tolerated in this double-blind study. Results support the clinical utility of this new once-daily formulation." ]

[ "8569016", "8178840", "11226444", "3828253", "16315025", "2548135", "12627044", "7641897", "8487239" ]

[ "Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial.", "Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group.", "Constant estrogen, intermittent progestogen vs. continuous combined hormone replacement therapy: tolerability and effect on vasomotor symptoms.", "Continuous oestrogen-progestogen treatment and serum lipoproteins in postmenopausal women.", "Effects of two different regimens of continuous hormone replacement therapy on endometrial histopathology and postmenopausal uterine bleeding.", "A prospective 1-year study of estrogen and progestin in postmenopausal women: effects on the endometrium.", "Comparison of the difference in histopathology and cell cycle kinetics among the postmenopausal endometrium treated with different progestins in sequential-combined hormone replacement therapy.", "Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial.", "Evaluation of low-dose estrogen and progestin therapy in postmenopausal women. A double-blind, prospective study of sequential versus continuous therapy." ]

[ "To report the histological findings of the endometrium of postmenopausal women who were randomized to receive placebo, estrogen only, or one of three estrogen plus progestin (E+P) regimens in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.\n A 3-year multicenter, randomized, double-masked, placebo-controlled trial.\n A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy.\n Participants were randomized and stratified in equal numbers to one of the following treatments in 28-day cycles: placebo, 0.625 mg/d of conjugated equine estrogens (CEE), 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate (MPA) for the first 12 days, 0.625 mg/d of CEE plus 2.5 mg/d of MPA, or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone (MP) for the first 12 days.\n Histology of endometrium collected at baseline, annual, or unscheduled visits by biopsy, curettage, or hysterectomy.\n Intention to treat.\n During follow-up women assigned to estrogen alone were more likely to develop simple (cystic), complex (adenomatous), or atypical hyperplasia than those given placebo (27.7% vs 0.8%, 22.7% vs 0.8%, and 11.8% vs 0%, respectively) for the same types of hyperplasia (P < .001). Participants administered one of the three E+P regimens had similar rates of hyperplasia as those given placebo (P = .16). The occurrence of hyperplasia was distributed evenly across the 3 years of the trial. Women taking estrogens alone also had more unscheduled biopsies (66.4% vs 8.4%; P < .001) and curettages (17.6% vs 0.8%; P < .001) than women receiving placebo. The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens (P = .38). Of the 45 women with complex (adenomatous) or atypical hyperplasia, study medications were discontinued in all, and the biopsy results of 34 (94%) of 36 women with hyperplasia reverted to normal with progestin therapy. The remainder had dilatation and curettage (n = 2) or hysterectomy with (n = 2) or without (n = 6) prior medical therapy, or refused further biopsies (n = 1). One woman developed adenocarcinoma of the endometrium while receiving placebo.\n At a dosage of 0.625 mg, the daily administration of CEE enhanced the development of endometrial hyperplasia. Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only therapy.", "We evaluated four oral combinations of conjugated estrogens (Premarin) and medroxyprogesterone acetate in preventing endometrial hyperplasia, which can occur with conjugated estrogens alone.\n This was a 1-year prospective, double-blind, randomized, multicenter study in 1724 postmenopausal women. All five groups took conjugated estrogens (0.625 mg) daily. The respective medroxyprogesterone acetate dosages were 2.5 and 5.0 mg daily (groups A and B) and 5.0 and 10.0 mg for 14 days per 28-day cycle (groups C and D).\n Among the 1385 patients with valid biopsy data, endometrial hyperplasia developed in 20% in the conjugated estrogens-treated group and < or = 1% in each of the four conjugated estrogens/medroxyprogesterone acetate-treated groups. The incidence of endometrial hyperplasia did not differ significantly between any of the conjugated estrogens/medroxyprogesterone acetate regimens. However, none of the patients receiving the two higher medroxyprogesterone acetate dosages (groups B and D) had endometrial hyperplasia.\n The endometrial hyperplasia incidence was significantly lower in women treated with conjugated estrogens and medroxyprogesterone acetate than in women treated with conjugated estrogens alone.", "To compare the efficacy and tolerability of a novel oral constant estrogen plus intermittent progestogen hormone replacement therapy (HRT) regimen to a continuous combined HRT regimen in postmenopausal women.\n Subjects were randomly assigned to receive treatment with either constant 17beta-estradiol (E2), 1 mg, plus intermittent norgestimate (NGM) 90 microg (3 days off, 3 days on) (n=221) or E2 2 mg/norethisterone acetate (NETA) 1 mg (n=217) for 1 year. Treatments were evaluated based on the incidence of hot flushes and uterine bleeding.\n Both regimens had similar bleeding profiles and provided comparable vasomotor symptom relief. However, breast discomfort and edema were experienced by twice as many subjects who received E2/NETA.\n The constant E2/intermittent NGM regimen was well tolerated and possesses similar efficacy compared with a continuous combined E2/NETA regimen and may be considered whenever HRT without withdrawal bleeding is deemed appropriate.", "Serum lipids and lipoproteins were examined in 44 healthy postmenopausal women every 3 months during 1 year of treatment with either continuous oestrogen-norethisterone acetate or placebo. Total serum cholesterol and LDL-cholesterol levels were reduced by approximately 15% and 20% (P less than 0.001), respectively in the hormone group but were unchanged in the placebo group. Serum triglycerides levels remained constant in both groups. HDL-cholesterol levels were significantly reduced by approximately 10% in the hormone group but significant reductions of 5-10% also occurred in the placebo group so that differences between the two groups were only significant after 3 months of treatment. Vaginal bleedings were experienced during the first 3 months by eight of the 21 women receiving hormones, but in only one woman after 9 months of therapy. The addition of norethisterone acetate to postmenopausal oestrogen therapy in clinically relevant doses had no adverse effects on lipoproteins as previously reported, even though administered continuously. Moreover, the low frequency of bleeding with continuous oestrogen-progestogen therapy would make this an appropriate alternative in postmenopausal replacement therapy.", "To compare the effects of frequently used two different regimens of combined continuous hormone replacement therapy; 0.625 mg conjugated equine estrogen (CEE) + 2.5 mg medroxyprogesterone acetate (MPA) and 1 mg 17beta estradiol (E2) + 0.5 mg norethindrone acetate (NETA), on endometrial histopathology and postmenopausal uterine bleeding.\n Two hundred and forty-six outpatient subjects aged 41-57 years were enrolled in the study conducted at the menopause clinic between November 2003 and November 2004. One hundred and thirty-nine patients were assigned to receive 0.625 mg conjugated equine estrogen + 2.5 mg medroxyprogesterone acetate (CEE/MPA), whereas 107 patients were to receive 17beta estradiol + 0.5 mg norethindrone acetate (E2/NETA). Inclusion criteria of the study were: normal values of endometrial thickness at basal evaluation, women with intact uterus, at least 12 months of amenorrhea, normal vaginal smear, bilateral mammography and biochemical blood parameters. All women were questioned every 3 months for vaginal bleeding/spotting. Endometrial sampling was performed by Pipelle catheter in the 12th month of therapy.\n For the first 3 months, vaginal bleeding/spotting rate for the CEE/MPA group was 38.7%, whereas it was higher (45%) in the E2/NETA group. For the second 3-month period, vaginal bleeding/spotting frequencies were 41.1 and 37.8%, respectively. In the third 3-month period 30.6 and 29.6%, and in the fourth 3-month period, 18.5 and 12.5% of the patients reported vaginal bleeding or spotting. None of the results of endometrial sampling have shown findings of cancer histopathology.\n Compared to CEE/MPA regimen, E2/NETA therapy has not shown more favorable effects on postmenopausal bleeding abnormalities. Irregular endometrial proliferation was seen more with the E2/NETA regimen.", "The endometrial response to oral, cyclic conjugated equine estrogens with and without the randomized addition of medroxyprogesterone acetate was evaluated in 95 postmenopausal women with respect to morphology and bleeding patterns. At 1 year, therapy with 0.625 mg conjugated equine estrogens or 1.25 mg conjugated equine estrogens for 25 days of a 30-day cycle and 5 mg medroxyprogesterone acetate added to the last 11 days of the conjugated equine estrogens cycle was associated with hyperplasia in 0 and 10% of the patients, respectively (P = not significant). Hyperplasia developed in 30 and 57% of the patients who received the above conjugated equine estrogens and placebo regimens, respectively. Irregular, breakthrough bleeding occurred in 14% of the conjugated equine estrogens/medroxyprogesterone acetate users and in 54% of the conjugated equine estrogens/placebo users. The results of this study indicate that 1 year of therapy with 0.625 mg conjugated equine estrogens and 5 mg medroxyprogesterone acetate provided the most satisfactory endometrial protection against hyperplasia and was associated with relatively low rates of breakthrough bleeding.", "To investigate the difference in histopathology and cell cycle kinetics in the menopausal endometrium treated with sequential-combined hormone replacement therapy (HRT) using different types and doses of progestins.\n A randomized, double-blind, 1-year study was conducted. In a menopause clinic of a university hospital, 241 postmenopausal women using HRT were included for the study of histopathology and cell cycle analysis. Conjugated equine estrogens, 0.625mg/day, were administered for 25 days (days 1-25) of each month, and the following were also administered for 14 days (days 12-25): in group A ( n= 102), medroxyprogesterone acetate (MPA), 5 mg/day; in group B ( n= 66), MPA, 10mg/day; and in group C ( n= 73), dydrogesterone, 20mg/day. Endometrial sampling was performed after at least 10 months of treatment. Fifty-two premenopausal women were also enrolled for the comparative studies (group Y). The S-G2-M fractions in the cell cycle were used as the marker of proliferation.\n Most menopausal endometria were normal regardless of the regimens of HRT. Endometrial hyperplasia was only found in two cases (both in group A). The S-G2-M fractions of the endometrial cells in all three menopausal groups showed no statistically significant difference. It appeared that S-G2-M fractions increased from normal postmenopausal to normal premenopausal endometria to postmenopausal hyperplasia to premenopausal hyperplasia. The S-G2-M fractions of the normal menopausal endometrial cells were lower than those of the premenopausal controls either in normal or in hyperplastic categories.\n Our study showed that there is no difference between the effect of MPA and dydrogesterone used in sequential-combined HRT based on the cycle kinetics of the menopausal endometrium.", "To determine whether treatment of endometriosis with a GnRH analogue (GnRH-a; goserelin) combined with continuous estrogen and progestogen hormone replacement therapy (HRT) would prevent the hypoestrogenic effects, including loss of bone density, while maintaining efficacy for treatment of endometriosis.\n Randomized controlled trial.\n Fifty premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Score for endometriosis implants equal to four or greater) and significant symptoms of dysmenorrhoea, dyspareunia, and other pelvic pain.\n Patients were randomized to receive either goserelin alone, 3.6 mg SC depot every 4 weeks for 24 weeks, or goserelin, 3.6 mg SC depot every 4 weeks for 24 weeks, plus HRT (25 micrograms transdermal 17 beta E2 daily and 5 mg medroxyprogesterone acetate orally daily) for 20 weeks commencing with the second goserelin injection.\n There was a significant reduction in the extent of pelvic endometriosis in both groups, with no difference between the groups. Both groups experienced an improvement in symptoms and signs, again with no difference between groups. Hypoestrogenic side effects of hot flushes and loss of libido were significantly less in the group that received HRT. The amount of bone mineral density loss was significantly less in the HRT group at the lumbar spine, although it was not prevented completely.\n The addition of HRT to GnRH-a for the treatment of endometriosis did not reduce the efficacy of treatment, and adverse hypoestrogenic effects were decreased, although not abolished.", "In this prospective, double-blind study, we evaluated the efficacy and safety of low-dose estrogen and progestin replacement therapy in 36 postmenopausal women who were administered oral medroxyprogesterone acetate (MPA) cyclically or continuously in combination with conjugated equine estrogen (CEE) 0.625 mg daily. In the sequential group, MPA (5.0 mg) was administered daily for 12 days of each 25-day treatment cycle. In the two continuous groups, MPA was administered without interruption at a daily dose of either 2.5 mg or 5.0 mg for 12 treatment cycles. Of the 36 women in the study, 29 women completed the one-year protocol. The clinical and metabolic responses were assessed before and every three cycles during the 12 cycles of treatment. Endometrial biopsies and lumbar bone density scans were performed before and during the last week of the 12th treatment cycle. Vasomotor and urogenital symptoms improved in all women. Cyclic menstrual bleeding occurred in all patients on sequential therapy, and proliferative endometrium was noted in two of these women. All patients in both continuous treatment groups experienced amenorrhea after the fifth cycle of therapy, and all endometrial biopsies were atrophic or inactive. From the 3rd through the 12th month of cycle, favorable lipid and lipoprotein changes occurred in all treatment groups. Lumbar bone mineral density improved significantly (P < .05) by an average of 6.41% in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "12510471", "15831542", "7823387", "10230742", "18851769", "12694632", "2809052", "11730399", "9292842" ]

[ "Effectiveness of prompted voiding in treating urinary incontinence in cognitively impaired homebound older adults.", "Failure of Internet-based audit and feedback to improve quality of care delivered by primary care residents.", "Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.", "A randomized trial of a computer-based intervention to reduce utilization of redundant laboratory tests.", "Use of a time series design to test effectiveness of a theory-based intervention targeting adherence of health professionals to a clinical guideline.", "Randomised controlled trial of a theoretically grounded tailored intervention to diffuse evidence-based public health practice [ISRCTN23257060].", "Prompted voiding treatment of urinary incontinence in nursing home patients. A behavior management approach for nursing home staff.", "Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses.", "A randomized trial of \"corollary orders\" to prevent errors of omission." ]

[ "The objective of this study was to examine the short-term effectiveness of prompted voiding (PV) in cognitively impaired homebound older adults.\n This was a prospective, controlled exploratory study with a cross-over design where usual care controls crossed-over to the intervention following an 8-week observation period.\n Adults aged 60 years and older with urinary incontinence and who met Center for Medicare and Medicaid Services criteria for being homebound were referred to the study by home care nurses from 2 large Medicare-approved home health agencies in a large metropolitan county in southwestern Pennsylvania. Nineteen cognitively impaired older adults were randomly assigned to either the PV intervention or a usual care attention control group.\n Measures used included structured continence and medical histories. Older American Research and Service Physical and Instrumental Activities of Daily Living scales, Folstein Mini Mental State Examination, Clock Drawing Test, Geriatric Depression Scale, Performance-Based Toileting Assessment, bladder diaries, and physical examination.\n Nineteen subjects were randomly assigned to a PV (n = 9) or delayed attention-control group (n = 10). Treatment subjects with complete pretreatment and posttreatment data (n = 6) experienced a mean 60% reduction in daytime incontinent episodes compared with a mean 37% reduction among control subjects (n = 10). Following the control phase, subjects crossed over to the treatment protocol. A total of 15 subjects completed the PV protocol. Among all subjects completing the treatment protocol, there was a 22% reduction in daytime incontinent episodes compared with true baseline (immediately following the control phase for those crossing over from the control group).\n The PV intervention resulted in clinically significant reductions in urinary incontinence for many of the participants, which may be achievable for many cognitively impaired homebound older adults.", "To determine the effectiveness of Internet-based audit and feedback to physicians to improve care for diabetes and hypertension.\n Time-series analysis of an intervention.\n The study setting was Harvard Vanguard Medical Associates, a 14-site multispecialty group in greater Boston. The study period was July 1997-June 1999.\n were 12 primary care internal medicine residents who provided care to adult patients with diabetes (n = 76 pre-intervention and n = 88 post-intervention), hypertension (n = 329 pre-intervention and n = 338 post-intervention), or both (n = 62 pre-intervention and n = 71 post-intervention). We determined the proportion of each resident's patients whose care fulfilled national guidelines for quality (i.e. diabetes patients had hemoglobin testing in the previous 6 months or hypertension patients received a beta-blocker or diuretic in the same time period). After meeting individually with each resident to obtain informed consent and to encourage participation, we sent each resident information for accessing his or her practice profile on a secure website. The main outcome measures were (i) the proportion of resident physicians who accessed their profiles and (ii) change following the intervention in the proportion of patients whose care followed national guidelines.\n Over a 1-year period, only four of the 12 residents accessed their websites. One of the residents visited her site three times, while the other three residents visited their sites once each. In interrupted time-series analyses, the intervention had no discernible effect on adherence to practice guidelines for diabetes or hypertension.\n The lack of participation in this Internet-based intervention may have important implications for the development of future programs that require physicians to interact with technology to improve quality of care.", "To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects.\n An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects.\n Meta-analyses from the Cochrane Pregnancy and Childbirth Database.\n The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding.\n Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%.\n This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.", "To determine the impact of giving physicians computerized reminders about apparently redundant clinical laboratory tests.\n We performed a prospective randomized controlled trial that included all inpatients at a large teaching hospital during a 15-week period. The intervention consisted of computerized reminders at the time a test was ordered that appeared to be redundant. Main outcome measures were the proportions of clinical laboratory orders that were canceled and the proportion of the tests that were actually performed.\n During the study period, there were 939 apparently redundant laboratory tests among the 77,609 study tests that were ordered among the intervention (n = 5,700 patients) and control (n = 5,886 patients) groups. In the intervention group, 69% (300 of 437) of tests were canceled in response to reminders. Of 137 overrides, 41% appeared to be justified based on chart review. In the control group, 51% of ordered redundant tests were performed, whereas in the intervention group only 27% of ordered redundant tests were performed (P <0.001). However, the estimated annual savings in laboratory charges was only $35,000. This occurred because only 44% of redundant tests performed had computer orders, because only half the computer orders were screened for redundancy, and because almost one-third of the reminders were overridden.\n Reminders about orders for apparently redundant laboratory tests were effective when delivered. However, the overall effect was limited because many tests were performed without corresponding computer orders, and many orders were not screened for redundancy.", "The aim of this study was to test the effectiveness of a theory of planned behaviour intervention to increase adherence of community mental health professionals to a national suicide prevention guideline.\n Routinely collected audit adherence data from an intervention and control site were collected and analysed using time series analysis to test whether the intervention significantly increased adherence. The effects of a local and national event on adherence were also examined.\n A Theory of Planned Behaviour (TPB) questionnaire, developed from interview findings, was administered to the health professionals. Subjective norms were found to be the most significant predictor of intention to adhere to the guideline, and were targeted with an interactive educational intervention. Time series analysis applied to routinely collected audit adherence data was used to test intervention effectiveness.\n The TPB accounted for 58% of the variance in intention to adhere, with subjective norms the only significant predictor. The intervention did not significantly increase adherence; however, the national and local events were found to have significantly increased adherence.\n The TPB was a useful framework for exploring barriers to adherence; however, this did not translate into an effective intervention. Future research should seek collaboration with local experts, and use this information in combination with the TPB, to develop interventions. Collaborative research with experts in pedagogy may also help to develop more effective interventions, particularly education-based interventions that require adult learning.", "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.", "This study evaluated a treatment procedure in which 126 incontinent nursing home patients were checked on an hourly basis, asked if they needed toileting assistance (prompted), and socially reinforced for appropriate toileting. Urodynamic analysis (including cystometrogram), provocative stress test, and behavioral assessment revealed that the nursing home patients were severely debilitated, with 65% demonstrating bladder abnormalities, 87% incapable of independent toileting, and 25% failing to score on the Mini-Mental Status Exam (average score, 8.0). The treatment procedures were evaluated with a multiple baseline design in which subjects were randomly divided into immediate or delayed treatment groups after a baseline observation period. During treatment, the frequency of incontinence per 12 hours changed from a baseline average of 3.85 to a treatment average of 1.91. Three behavioral measures that can be easily collected by nursing staff significantly predicted continence levels during treatment (multiple R, 0.79) and change in incontinence during treatment (multiple R, 0.64). These prognostic criteria offer nursing staff a cost-effective method for selecting the most responsive patients for prompted-voiding treatment.", "To explore whether reported methodologic quality affects estimated intervention effects in randomized trials and contributes to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.\n Meta-analyses of randomized trials that included at least one large trial (>/=1000 participants) were included, regardless of the therapeutic area. Eligible meta-analyses were identified through electronic searches and bibliographies of relevant articles.\n Full-length randomized trials.\n Methodologic quality was assessed according to reported randomization, double blinding, and follow-up as separate components and by using the Jadad composite scale.\n Fourteen meta-analyses involving 190 randomized trials from eight therapeutic areas were included. Compared with large trials, intervention effects were exaggerated in small trials with inadequate allocation sequence generation (ratio of odds ratios, 0.46 [95% CI, 0.25 to 0.83]; P = 0.011), inadequate allocation concealment (ratio of odds ratios, 0.49 [CI, 0.27 to 0.86]; P = 0.014), and no double blinding (ratio of odds ratios, 0.52 [CI, 0.28 to 0.96]; P = 0.01). Large trials did not differ significantly from small trials with adequate generation of the allocation sequence, adequate allocation concealment, or adequate double blinding. No association was seen between reported follow-up and intervention effects. The Jadad scale provided no additional information because the scale and the quality components overlapped substantially.\n Inadequate generation of the allocation sequence, allocation concealment, and double blinding lead to exaggerated estimates of intervention benefit and may contribute to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.", "Errors of omission are a common cause of systems failures. Physicians often fail to order tests or treatments needed to monitor/ameliorate the effects of other tests or treatments. The authors hypothesized that automated, guideline-based reminders to physicians, provided as they wrote orders, could reduce these omissions.\n The study was performed on the inpatient general medicine ward of a public teaching hospital. Faculty and housestaff from the Indiana University School of Medicine, who used computer workstations to write orders, were randomized to intervention and control groups. As intervention physicians wrote orders for 1 of 87 selected tests or treatments, the computer suggested corollary orders needed to detect or ameliorate adverse reactions to the trigger orders. The physicians could accept or reject these suggestions.\n During the 6-month trial, reminders about corollary orders were presented to 48 intervention physicians and withheld from 41 control physicians. Intervention physicians ordered the suggested corollary orders in 46.3% of instances when they received a reminder, compared with 21.9% compliance by control physicians (p < 0.0001). Physicians discriminated in their acceptance of suggested orders, readily accepting some while rejecting others. There were one third fewer interventions initiated by pharmacists with physicians in the intervention than control groups.\n This study demonstrates that physician workstations, linked to a comprehensive electronic medical record, can be an efficient means for decreasing errors of omissions and improving adherence to practice guidelines." ]

[ "7818255", "11591843", "15557491", "9820296", "18635256", "15090564", "19949030", "9093250", "17623736" ]

[ "Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis.", "Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS.", "Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study.", "Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS.", "Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial.", "Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis.", "A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS.", "Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis.", "Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study." ]

[ "A randomized, double-blinded, placebo-controlled, clinical trial of low-dose, weekly, oral methotrexate was performed in 60 patients with clinically definite chronic progressive multiple sclerosis (MS) attending a referral-based outpatient MS clinic. Study patients were 21 to 60 years old with a disease duration of longer than 1 year. Patients' Expanded Disability Status Scale scores were 3.0 to 6.5 (ambulatory with moderate disability). Patients were first stratified by Expanded Disability Status Scale scores, 3.0 to 5.5 and 6.0 to 6.5, and then were randomized to receive methotrexate or placebo treatment. Treatment consisted of weekly, oral, low-dose (7.5 mg) methotrexate or identical placebo for 2 years, followed by observation for as long as 1 year. A composite outcome measurement instrument was used and consisted of (1) Expanded Disability Status Scale, (2) ambulation index, (3) Box and Block Test, and (4) 9-Hole Peg Test. Failure of therapy was indicated by a designated change that was sustained for more than 2 months in one or more components of this composite measure. Significantly less progression of impairment as measured by validated tests of upper-extremity function was observed in the methotrexate treatment group in the absence of clinically significant toxicity. We conclude that low-dose, weekly, oral methotrexate offers a new, relatively nontoxic treatment option for patients with chronic progressive MS.", "IV methylprednisolone (IVMP) has been used to treat relapses in patients with relapsing-remitting (RR) MS, but its effect on disease progression is not known. Furthermore, there are no data on the impact of IVMP on T1 black holes or whole-brain atrophy.\n To determine the effect of IVMP on MRI measures of the destructive pathology in patients with RR-MS and secondarily to determine the effect of IVMP on disability progression in patients with RR-MS.\n The authors conducted a randomized, controlled, single-blind, phase II clinical trial of IVMP in patients with RR-MS. Eighty-eight patients with RR-MS with baseline Expanded Disability Status Scale (EDSS) scores of < or =5.5 were randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral prednisone taper) or IVMP at the same dose schedule only for relapses (IVMP for relapses) and followed without other disease-modifying drug therapy for 5 years. Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the subsequent 2 years. Patients had quantitative cranial MRI scans at study entry and after 5 years and standardized clinical assessments every 4 to 6 months.\n Eighty-one of 88 patients completed the trial as planned, and treatment was well tolerated. Baseline demographic, clinical, and MRI measures were well matched in the two study arms. Patients on the pulsed IVMP arm received more MP than patients on the control arm of the study (p < 0.0001). Mean change in T1 black hole volume favored pulsed IVMP therapy (+1.3 vs +5.2 mL; p < 0.0001), as did mean change in brain parenchymal volume (+2.6 vs -74.5 mL; p = 0.003). There was no significant difference between treatment arms in the change in T2 volume or annual relapse rate during the study. However, there was significantly more EDSS score worsening in the control group, receiving IVMP only for relapses. There was a 32.2% reduction (p </= 0.0001) in the probability of sustained EDSS score worsening in the pulsed MP arm compared with the relapse treatment arm. At the end of the study, EDSS was better in the pulsed MP group (1.7 vs 3.4; p < 0.0001). Prolonged treatment with pulsed IVMP was safe and well tolerated; only two patients dropped out for toxic side effects over 5 years.\n In patients with RR-MS, treatment with pulses of IVMP slows development of T1 black holes, prevents or delays whole-brain atrophy, and prevents or delays disability progression. A phase III study of IVMP pulses is warranted.", "To evaluate the efficacy and safety of interferon beta-1b (IFNbeta-1b) in subjects with secondary progressive multiple sclerosis (SPMS).\n This 3-year, multicenter, double-blind, placebo-controlled, randomized trial of IFNbeta-1b included 939 subjects from the United States and Canada with SPMS and Expanded Disability Status Scale (EDSS) scores ranging from 3.0 to 6.5. Subjects were randomly assigned to receive either placebo or IFNbeta-1b (250 microg or 160 microg/m2 body surface area), administered subcutaneously every other day. The primary outcome was time to progression by > or =1.0 EDSS point (0.5 point if EDSS score was 6.0 to 6.5 at entry) confirmed at 6 months. Secondary outcomes included mean change in EDSS score from baseline, relapse-related measures, MRI activity, and a standardized neuropsychological function test.\n There was no significant difference in time to confirmed progression of EDSS scores between placebo-treated patients and either of the IFNbeta-1b treatment groups. However, IFNbeta-1b treatment resulted in improvement on secondary outcome measures involving clinical relapses, newly active MRI lesions, and accumulated burden of disease on T2-weighted MRI. Effects were similar for both IFNbeta-1b treatment groups. Neutralizing antibodies to IFNbeta-1b were detected in 23% of 250-microg and 32% of 160-microg/m2 recipients, but their presence did not consistently affect clinical or MRI outcomes. IFNbeta-1b was also well tolerated at both doses.\n Although no treatment benefit was seen on the time to confirmed progression of disability, relapse- and MRI-related outcomes showed significant benefit with both dosing regimens tested, a result consistent with the outcomes of earlier clinical trials.", "The beneficial effects of interferon beta have only been shown for patients in the relapsing-remitting phase of multiple sclerosis (MS). The role of interferon beta in the treatment of patients who are in the secondary progressive phase of the disease (SP-MS), and for whom no effective drug treatment is available, has not been assessed.\n In this multicentre, double-masked, randomised, placebo-controlled trial, outpatients with SP-MS having scores of 3.0-6.5 on the Expanded Disability Status Scale (EDSS) received either 8 million IU interferon beta-1b every other day subcutaneously, or placebo, for up to 3 years. The primary outcome was the time to confirmed progression in disability as measured by a 1.0 point increase on the EDSS, sustained for at least 3 months, or a 0.5 point increase if the baseline EDSS was 6.0 or 6.5. A prospectively planned interim analysis of safety and efficacy of the intention-to-treat population was done after all patients had been in the study for at least 2 years.\n 358 patients with SP-MS were allocated placebo and 360 were allocated interferon beta-1b; 57 patients (31 placebo, 26 interferon beta-1b) were lost to follow-up. There was a highly significant difference in time to confirmed progression of disability in favour of interferon beta-1b (p=0.0008). Interferon beta-1b delayed progression for 9-12 months in a study period of 2-3 years. The odds ratio for confirmed progression was 0.65 (95% CI 0.52-0.83). This beneficial effect was seen in patients with superimposed relapses and in patients who had only progressive deterioration without relapses. Positive results were also obtained regarding time to becoming wheelchair-bound, relapse rate and severity, number of steroid treatments and hospital admissions, as well as on magnetic resonance imaging variables. The drug was safe and side effects were in line with previous experience with interferon beta-1b. The study was stopped after the interim results gave clear evidence of efficacy.\n Treatment with interferon beta-1b delays sustained neurological deterioration in patients with SP-MS. Interferon beta-1b is the first treatment to show a therapeutic effect in patients with SP-MS.", "Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis. The aim of the combination of methotrexate and etanercept in active early rheumatoid arthritis (COMET) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept.\n 542 outpatients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3-24 months were randomly assigned to receive either methotrexate alone titrated up from 7.5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate (same titration) plus etanercept 50 mg a week. Coprimary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints (DAS28) and radiographic non-progression measured with modified total Sharp score. Treatment was allocated with a computerised randomisation and enrolment system, which masked both participants and carers. Analysis was done by modified intention to treat with last observation carried forward for missing data. This study is registered with ClinicalTrials.gov, number NCT00195494).\n 274 participants were randomly assigned to receive combined treatment and 268 methotrexate alone. 132 of 265 (50%, 95% CI 44-56%) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 (28%, 23-33%) taking methotrexate alone (effect difference 22.05%, 95%CI 13.96-30.15%, p<0.0001). 487 evaluable patients had severe disease (DAS28>5.1). 196 of 246 (80%, 75-85%) and 135 of 230 (59%, 53-65%), respectively, achieved radiographic non-progression (20.98%, 12.97-29.09%, p<0.0001). Serious adverse events were similar between groups.\n Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate.\n Wyeth Research.", "Interferon (IFN) beta has repeatedly shown benefit in multiple sclerosis (MS) in reducing the rate of relapse, the disease activity as shown with magnetic resonance imaging and, to some degree, the progression of disability; however, it is unknown how much the therapeutic response depends on the dose, the subgroup involved, and the disease stage. This multicentre, double blind, placebo controlled study explored the dose-response curve by examining the clinical benefit of low dose IFN beta-1a (Rebif), 22 micro g subcutaneously once weekly, in patients with secondary progressive MS.\n A total of 371 patients with clinically definite SPMS were randomised to receive either placebo or subcutaneous IFN beta-1a, 22 micro g once weekly, for 3 years. Clinical assessments were performed every 6 months. The primary outcome was time to sustained disability, as defined by time to first confirmed 1.0 point increase on the Expanded Disability Status Scale (EDSS). Secondary outcomes included a sensitive disability measure and relapse rate.\n Treatment had no beneficial effect on time to confirmed progression on either the EDSS (hazard ratio (HR) = 1.13; 95% confidence interval (CI) 0.82 to 1.57; p = 0.45 for 22 micro g v placebo) or the Regional Functional Status Scale (HR = 0.93; 95% CI 0.68 to 1.28; p = 0.67). Other disability measures were also not significantly affected by treatment. Annual relapse rate was 0.27 with placebo and 0.25 with IFN (rate ratio = 0.90; 95% CI 0.64 to 1.27; p = 0.55). The drug was well tolerated with no new safety concerns identified. No significant gender differences were noted.\n This patient population was less clinically active than SPMS populations studied in other trials. Treatment with low dose, IFN beta-1a (Rebif) once weekly did not show any benefit in this study for either disability or relapse outcomes, including a subgroup with preceding relapses. These results add a point at one extreme of the dose-response spectrum of IFN beta therapy in MS, indicating that relapses in this phase may need treatment with higher doses than in the initial phases.", "To compare the efficacy, tolerability, and safety of IV methylprednisolone (IV MP) vs oral methylprednisolone (oMP) at equivalent high doses in patients with multiple sclerosis (MS) experiencing a recent relapse.\n Patients with a clinical relapse within the previous 2 weeks and at least 1 gadolinium (Gd)-enhancing lesion on a screening brain MRI scan were included. Forty patients with MS were randomized to receive either 1 g/day for 5 days of oMP (20 patients) or 1 g/day for 5 days of IV MP (20 patients). Expanded Disability Status Scale (EDSS) and brain MRI (dual-echo and postcontrast T1-weighted scans) were assessed at baseline and at weeks 1 and 4. The study primary research question (endpoint) was to compare the efficacy of the 2 treatment routes in reducing the number of Gd-enhancing lesions after 1 week from treatment initiation. Secondary outcomes were safety, tolerability, and clinical efficacy profiles of the 2 routes of administration.\n The 2 groups showed a reduction of Gd-enhancing lesions over time (p = 0.002 for oMP and p = 0.001 for IV MP) with a \"non-inferiority effect\" between the 2 routes of administration at week 1. Both groups showed an improvement of EDSS over time (p < 0.001) without between-group difference at week 4. Both treatments were well-tolerated and adverse events were minimal and occurred similarly in the 2 treatment arms.\n Oral methylprednisolone (oMP) is as effective as IV methylprednisolone in reducing gadolinium-enhancing lesions in patients with MS soon after an acute relapse with similar clinical, safety, and tolerability profiles. This study provides class III evidence that 1 g oMP x 5 days is not inferior to 1 g IV MP x 5 days in reducing the number of gadolinium-enhancing lesions over a period of 1 week (mean difference in lesion reduction comparing IV MP to oMP is -20%, 95% confidence interval -48% to + 5%).", "An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis (MS) despite the lack of evidence to support this route of administration. Our double-blind placebo-controlled randomised trial was designed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS.\n 42 patients with clinically definite relapse in MS received oral, and 38 intravenous, methylprednisolone. Clinical measurements at entry and at 1 week, 4 weeks, 12 weeks, and 24 weeks included Kurtzke's expanded disability status scale (EDSS), Hauser's Ambulatory Index, and an arm-function index. The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grades at 4 weeks.\n There were no significant differences between the two groups at any stage of the study in any measurement taken: the mean difference in EDSS at 4 weeks (adjusted for baseline level) was 0.07 grades more in those taking oral steroids (95% CI -0.46 to 0.60). The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment.\n Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience, safety, and cost.", "In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS (n=34) and SPMS (n=197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group (P=0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions. In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks (P=0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score. In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group (P=0.028). The difference was significant in PPMS (P=0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance (P=0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS." ]

[ "17065044", "21596735", "10485722", "9197872", "16616557", "15695996", "16641396", "19527380", "9241285" ]

[ "Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status.", "Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial.", "Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.", "Antioxidants in the treatment of severe pre-eclampsia: an explanatory randomised controlled trial.", "Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.", "Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial.", "Vitamins C and E and the risks of preeclampsia and perinatal complications.", "Comparison of effect of daily versus weekly iron supplementation during pregnancy on lipid peroxidation.", "Calcium supplementation and the risk of preeclampsia in Ecuadorian pregnant teenagers." ]

[ "To investigate maternal and neonatal outcomes after antioxidant supplementation relatively early in pregnancy (8 to 12 weeks) for pregnant women with low antioxidant status.\n A randomized, double-blind, placebo-controlled trial of daily antioxidant supplementation was performed on pregnant women screening positive for low antioxidant status at 8 to 12 weeks of gestation. Low antioxidant status was defined as a superoxidedismutase (SOD) level below 1102 U/g Hb or 164 U/mL. The supplementation group received the following antioxidants daily: vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 microg), C (200 mg), and E (400 IU), folic acid (400 microg), N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg), Fe (30 mg), calcium (800 mg), and selenium (100 microg). The control group received Fe (30 mg) and folic acid (400 microg). Maternal (preeclampsia, abortion, and hypertension) and perinatal outcomes were assessed.\n In the supplementation group (29 subjects), we observed 2 cases of preeclampsia (6.8%, 1 mild and 1 severe), 1 of IUGR (birth weight 2300 g at 38 weeks), and 1 preterm delivery. In the control group (31 subjects), there were 8 abortions, 9 cases of preeclampsia (29%, 6 mild and 3 severe) with perinatal outcome: 3 preterm delivery cases and 1 IUGR (birth weight 2030 g at 39 weeks). Preeclampsia was significantly less frequent in the supplementation group when compared to the control group (2 vs. 9 cases, p = 0.043, OR = 0.18 [95% CI: 0.03, 0.92]). Finally we focused on the prediction of preeclampsia at 8 to 12 weeks. Combined sensitivity of markers of antioxidant status (SOD slutathione peroxidase, [GPx], and total anti-oxidant status [TAS]) was 33% (false-positive rate of 4.5%).\n Antioxidant supplementation was associated with better maternal and perinatal outcome in pregnant women with low antioxidant status than control supplementation with iron and folate alone. In a selected population already screened positive for low SOD, preeclampsia can be detected in 33% of asymptomatic cases in the first trimester using SOD, GPx, and TAS. It seems feasible that panels of both biochemical and molecular markers may be clinically useful in the prediction of this disease.", "To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk.\n Randomised, blinded, placebo controlled clinical trial.\n Tertiary public hospital in Mexico City.\n Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery.\n Supplementation with a medical food-bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo-during pregnancy.\n Development of pre-eclampsia/eclampsia.\n 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ(2) = 19.41; P < 0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ(2) = 3.76; P = 0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P = 0.004; absolute risk reduction 0.09, 0.05 to 0.14).\n Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846.", "Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia.\n 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study.\n Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002).\n Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.", "To determine whether antioxidant therapy alters the disease process in severe early onset pre-eclampsia, in support of the hypothesis that increased lipid peroxides and reactive oxygen species production-play an important role in the pathogenesis of the disease.\n Randomised, double-blind, placebo controlled trial.\n Two tertiary care, referral hospitals in Johannesburg, South Africa.\n Women with severe pre-eclampsia diagnosed between 24 and 32 weeks of gestation.\n Combined antioxidant treatment with vitamin E (800 IU/day), vitamin C (1000 mg/day), and allopurinol (200 mg/day).\n Primary outcomes: 1. prolongation of pregnancy and 2, biochemical assessment of lipid peroxides and antioxidants. Secondary outcomes: data on maternal complications, side effects of treatment, infant outcomes and regular assessment of haematologic and renal parameters.\n The proportion of women delivered within 14 days in the antioxidant group was 52% (14/27) compared with 76% (22/29) in the placebo group (relative risk 0.68, 95% confidence interval 0.45-1.04). One woman in each group had eclampsia. Eleven women (42%) in the antioxidant and 16 (59%) in the placebo group required two antihypertensives for blood pressure control. Trial medications were well tolerated with few side effects. Lipid peroxide levels were not significantly altered in the antioxidant and placebo groups. Serum uric acid levels decreased and vitamin E levels increased significantly.\n The results of this explanatory randomised trial do not encourage the routine use of antioxidants against pre-eclampsia. However, further research with modified strategies such as earlier initiation of therapy or different combinations seem worthwhile.", "Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors.\n We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 .\n Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]).\n Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.", "We sought to determine the effect of supplemental antioxidant vitamins C and E on the rate of preeclampsia in high-risk pregnant women.\n Women at risk for preeclampsia (previous preeclampsia, chronic hypertension, pregestational diabetes, or multifetal gestation) were recruited at 14 to 20 weeks' gestation and randomly assigned to receive either 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily in addition to their regular prenatal vitamins. The primary outcome was the occurrence of preeclampsia. An estimated sample size of 220 women in each arm was determined to be necessary to demonstrate a 50% reduction in the rate of preeclampsia.\n Funding was terminated after 109 women had been recruited; 9 were lost to follow-up or withdrew. We analyzed data from the remaining 100 women to look for differences in outcome and to estimate the required sample size for future studies. The rate of preeclampsia was not different: 17.3% in women who received supplemental vitamins C and E, versus 18.8% in the placebo group. Assuming a baseline rate of preeclampsia in the placebo group between 15% and 20%, we can estimate that 500 to 950 women in each arm will be required to show a clinically important reduction in the rate of preeclampsia.\n The potential benefit of vitamin C and E supplementation to prevent preeclampsia in women with clinical risk factors is smaller than we estimated. Future studies of antioxidant vitamin supplementation in this population will require more than 500 women in each arm.", "Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.\n We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.\n Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).\n Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).\n Copyright 2006 Massachusetts Medical Society.", "To compare the effect of daily versus weekly iron supplementation on lipid peroxidation, hemoglobin levels and maternal and perinatal outcome in non-anemic pregnant women.\n Of 109 women randomly allocated into three groups, 90 completed the study. Group I (n = 30) received daily iron folic acid; Group II (n = 30) received weekly iron folic acid; Group III (n = 30) received daily iron (III)-hydroxide polymaltose complex. Hemoglobin levels, hematological indices, thiobarbituric acid reactive substances (TBARS) and glutathione levels were measured at baseline (14-16 weeks) and at 30-34 weeks. Statistical analysis was done using the anova test.\n Group I had a highly significant increase in TBARS level (0.61 +/- 0.26 micromol/L, P = 0.000) compared to groups II and III in which the change in TBARS was not significant (0.02 +/- 0.06 and 0.007 +/- 0.06 micromol/L, respectively). There was an insignificant fall in glutathione levels in all groups. There was no significant difference in the mean period of gestation, pregnancy complications and neonatal outcome between the three groups. Among 22.2% of women who were non-compliant, Group I had significantly higher incidence of non-compliance (P = 0.016) and side-effects (P = 0.001). Final hemoglobin was higher in Group I than II (11.9 +/- 1.2, 11.3 +/- 0.9, respectively, P = 0.041). The TBARS level was not statistically different between preterm and term deliveries. Nine out of 11 patients who developed hypertension during pregnancy had preeclampsia. The final TBARS level was significantly higher in these women (P = 0.000).\n Daily supplementation with ferrous sulphate results in greater lipid peroxidation than weekly supplementation, the latter is comparable with daily iron (III)-hydroxide polymaltose complex. Lipid peroxidation levels are significantly higher in preeclampsia.", "To determine whether increased calcium intake (2 g/day) in pregnancy is effective in reducing the risk of preeclampsia in pregnant teenagers.\n The present study was a prospective, randomized, double-blind, controlled clinical trial. Two hundred sixty teenaged pregnant girls attending the Hospital Gíneco-Obstétrico Isidro Ayora in Quito, Ecuador, were included. Selection criteria were age less than 17.5 years, nulliparity, first prenatal visit before 20 weeks' gestation, and residency in Quito (2800-m altitude). We used a table of random numbers to assign 125 girls to receive 2000 mg of elemental calcium daily, beginning at 20 weeks of gestation and continuing until delivery; 135 women in the control group received a placebo. Blood pressure (BP) was measured twice every 4 weeks until delivery and at 48 hours after delivery. The diagnosis of preeclampsia was defined as BP greater than 140/90 mmHg on at least two occasions more than 6 hours apart and proteinuria greater than 30 mg/dL (over one cross by dipstick on two occasions 4-24 hours apart).\n The average daily calcium intake in this population was approximately 51% of the Recommended Dietary Allowance. Calcium supplementation was associated with a significantly decreased risk of preeclampsia (risk reduction 12.35%; P < .001), with 3.2% (n = 4) developing preeclampsia in the treatment group versus 15.5% (n = 21) in the placebo group. Moreover, calcium supplementation led to a reduction in systolic BP of 9.1 mmHg and in diastolic BP of 6.0 mmHg.\n These results suggest that calcium supplementation during pregnancy in populations with low calcium intake is a safe, effective, and inexpensive preventive measure that significantly reduces the risk of preeclampsia." ]

[ "9642605", "8238130", "18472878", "16832124", "1407911", "11293641", "8238160", "9307346", "10461843" ]

[ "Antibiotic treatment in preterm labor and intact membranes: a randomized, double-blinded, placebo-controlled trial.", "Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.", "Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor.", "A randomized controlled trial of prophylactic antibiotics (co-amoxiclav) prior to embryo transfer.", "Expectant management of preterm ruptured membranes: effects of antimicrobial therapy.", "Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group.", "Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture.", "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.", "Vaginal disinfection with chlorhexidine during childbirth." ]

[ "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.", "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.", "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.", "Bacterial contamination of the transfer catheter during embryo transfer is associated with poor clinical outcomes. Antibiotics at the time of embryo transfer may improve outcomes. We evaluated the effect of co-amoxiclav on the rates of bacterial contamination of transfer catheters and clinical pregnancy.\n On the day of oocyte collection, 350 patients were randomized, with sequentially numbered opaque-sealed envelopes containing treatment allocation assigned randomly by computer, to receive co-amoxiclav on the day before and the day of embryo transfer, or no antibiotics. Following transfer, the catheter tips were cultured and assessed to identify the organism(s) isolated and to quantify the level of the contamination. Couples were followed for 8 weeks to determine whether they had achieved clinical pregnancy. Outcome assessors were blinded to the treatment allocation, and the analysis was by intention to treat.\n Antibiotics significantly reduced catheter contamination rates (49.4 versus 62.3%, RR = 0.79, 95% CI: 0.64, 0.97, P = 0.03). There was no difference detected in clinical pregnancy rates between the two groups (36.0 versus 35.5%, P = 0.83) although there was a significant (P = 0.03) association between the level of bacterial contamination and clinical pregnancy rates.\n Co-amoxiclav reduces catheter contamination, but this is not translated into better clinically relevant outcomes such as clinical pregnancy rates. Our findings do not support the routine use of antibiotics at embryo transfer.", "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.", "Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue.\n 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat.\n None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection.\n This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.", "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.", "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.", "The purpose of this study was to determine whether chlorhexidine vaginal douching, applied by a squeeze bottle intra partum, reduced mother-to-child transmission of vaginal microorganisms including Streptococcus agalactiae (streptococcus serogroup B = GBS) and hence infectious morbidity in both mother and child. A prospective controlled study was conducted on pairs of mothers and their offspring. During the first 4 months (reference phase), the vaginal flora of women in labour was recorded and the newborns monitored. During the next 5 months (intervention phase), a trial of randomized, blinded placebo controlled douching with either 0.2% chlorhexidine or sterile saline was performed on 1130 women in vaginal labour. During childbirth, bacteria were isolated from 78% of the women. Vertical transmission of microbes occurred in 43% of the reference deliveries. In the double blind study, vaginal douching with chlorhexidine significantly reduced the vertical transmission rate from 35% (saline) to 18% (chlorhexidine), (P < 0.000 1, 95% confidence interval 0.12-0.22). The lower rate of bacteria isolated from the latter group was accompanied by a significantly reduced early infectious morbidity in the neonates (P < 0.05, 95% confidence interval 0.00-0.06). This finding was particularly pronounced in Str. agalactiae infections (P < 0.0 1). In the early postpartum period, fever in the mothers was significantly lower in the patients offered vaginal disinfection, a reduction from 7.2% in those douched using saline compared with 3.3% in those disinfected using chlorhexidine (P < 0.05, 95% confidence interval 0.01-0.06). A parallel lower occurrence of urinary tract infections was also observed, 6.2% in the saline group as compared with 3.4% in the chlorhexidine group (P < 0.01, 95% confidence p interval 0.00-0.05). This prospective controlled trial demonstrated that vaginal douching with 0.2% chlorhexidine during labour can significantly reduce both maternal and early neonatal infectious morbidity. The squeeze bottle procedure was simple, quick, and well tolerated. The beneficial effect may be ascribed both to mechanical cleansing by liquid flow and to the disinfective action of chlorhexidine." ]

[ "12548322", "48000", "3959016", "8598837", "12521850", "8827572", "9621474", "16880306", "7052115" ]

[ "A randomized controlled trial of outpatient versus inpatient labour induction with vaginal controlled-release prostaglandin-E2: effectiveness and satisfaction.", "Elective induction of labour. A randomised prospective trial.", "Induction of labor with an electric breast pump.", "Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group.", "Induction of labour: a comparison of two methods with particular concern to patient acceptability.", "Controlled comparison of induction versus expectant care for prelabor rupture of the membranes at term.", "Induction of labor by intracervical prostaglandin gel and oxytocin infusion in primigravid women with unfavorable cervix.", "Morning compared with evening induction of labor: a nested randomized controlled trial. A nested randomized controlled trial.", "Induction of labour: a comparison of a single prostaglandin E2 vaginal tablet with amniotomy and intravenous oxytocin." ]

[ "Outpatient management in obstetrics is expanding, but evidence to support outpatient labour induction is needed.\n To compare the effectiveness, acceptability, duration of hospitalization, and safety of outpatient and inpatient induction of labour with intravaginal controlled-release prosta-glandin-E2 (CR-PGE2).\n A prospective, randomized, controlled trial enrolled 300 women at term with parity < or = 5 and singleton pregnancies in cephalic presentation. Each had an unscarred uterus, a normal non-stress test (NST), and a Bishop score of < or = 6. After insertion of the CR-PGE2, and 1 hour of monitoring, those in the outpatient group were discharged home, to return with onset of labour or 12 hours later for an NST. If not already in labour 24 hours later, the women returned for inpatient induction. Vaginal examination was not repeated before 24 hours unless the patient was contracting and required analgesia. Inpatients remained on the antepartum ward but were otherwise treated similarly. The women in both groups reported ratings of satisfaction, pain, and anxiety over the telephone until they were in labour.\n There were 150 women randomized to outpatient and 150 women to inpatient induction of labour. The number of women who were in labour or who delivered by 24 hours in the outpatient group was 115 (0.77, 95% confidence interval [CI] 0.70-0.84) and in the inpatient group was 107 (0.72, 95% CI 0.64-0.79). The median times to labour were 9.8 hours (95% CI, 8.1-11.4) and 11.4 hours (95% CI, 10.1-12.7), and to delivery were 21.4 hours (95% CI, 19.2-23.5) and 20.7 hours (95% CI, 18.4-23.0), for the outpatient and inpatient groups, respectively. In the outpatient group, 56% of women reported high satisfaction during the initial 12 hours of induction compared to 39% in the inpatient group (p < 0.008). Ratings of pain and anxiety during the first 12 hours of induction were similar. In the outpatient group, women were at home for a median of 8 hours (95% CI, 6.7-9.4) before labour and delivery. There were no significant differences in adverse outcomes.\n This study suggests that outpatient induction of labour with intravaginal CR-PGE2 may be a reasonable option for selected low-risk women; however, further study is needed to confirm the safety of this approach.", "In a prospective, randomised trial, 111 obstetrically normal pregnant women, who had elective induction of labour performed between 39 and 40 weeks, were compared with 117 controls who were managed expectantly until 41 weeks. Compared with the controls, the patients who had elective induction of labour had significantly less meconium staining in labour and a smaller blood-loss after delivery. The mean length of labour, the amount of pethidine used, and the Apgar scores at 1 minute were similar in the two groups. In the electively induced group, the caesarean-section rate was lower and the use of epidural analgesia more common than in the controls, but the differences were mot statistically signficant. The hour of delivery was similar in the two groups, suggesting that convenience to medical and nursing staff would not be greatly changed by elective induction of labour. There was no evidence that the hazards to mother and child were increased by elective induction, and its use might improve perinatal mortality by reducing the number of unexplained mature stillbirths.", "Nipple stimulation with an electric breast pump was compared with oxytocin infusion as a means of labor induction. The time from stimulation to the onset of regular uterine activity and to 200 Montevideo units of uterine activity and the time until entrance into the active phase of labor were significantly shorter in the nipple stimulation group. Once the women were in active labor, there was no difference between the groups in the length of labor or mode of delivery.", "As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. It is not known whether inducing labor will reduce this risk or whether one method of induction is better then another.\n We studied 5041 women with prelabor rupture of the membranes at term. The women were randomly assigned to induction of labor with intravenous oxytocin; induction of labor with vaginal prostaglandin E2 gel; or expectant management for up to four days, with labor induced with either intravenous oxytocin or vaginal prostaglandin E2 gel if complications developed. The primary outcome was neonatal infection. Secondary outcomes were the need for cesarean section and women's evaluations of their treatment.\n The rates of neonatal infection and cesarean section were not significantly different among the study groups. The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group, 3.0 percent for the induction-with-prostaglandin group, 2.8 percent for the expectant-management (oxytocin) group, and 2.7 percent for the expectant-management (prostaglandin) group. The rates of cesarean section ranged from 9.6 to 10.9 percent. Clinical chorioamnionitis was less likely to develop in the women in the induction-with-oxytocin group than in those in the expectant-management (oxytocin) group (4.0 percent vs. 8.6 percent, P<0.001), as was postpartum fever (1.9 percent vs. 3.6 percent, P=0.008). Women in the induction groups were less likely to say they liked \"nothing\" about their treatment than those in the expectant-management groups.\n In women with prelabor rupture of the membranes at term, induction of labor with oxytocin or prostaglandin E2 and expectant management result in similar rates of neonatal infection and cesarean section. Induction of labor with intravenous oxytocin results in a lower risk of maternal infection than does expectant management. Women view induction of labor more positively than expectant management.", "Induction of labour is a common obstetric intervention. When the cervix is unfavourable ripening agents are used, commonly prostaglandin E2. There are several methods of administration of prostaglandin E2 and little comparative work has been performed as to their acceptability by patients. Patients undergoing induction of labour by prostaglandin E2 were randomised to receive either intravaginal gel or an intravaginal slow-release pessary. Patient satisfaction with the method received was then assessed. Sixty-nine patients were randomised, 34 to receive gel and 35 to receive a pessary. Median scores for satisfaction of the induction process were the same for both methods; however, satisfaction with the labour was increased with those who had been randomised to the pessary group (median pessary=5, gel=4). There may be a marginal improvement in patient satisfaction when a slow-release intravaginal prostaglandin E2 pessary is used for the induction of labour.", "This randomized clinical trial compared oxytocin induction of labor with expectant care for 48 hours after prelabor rupture of the membranes at term. Women at term with prelabor rupture of the membranes for at least 8 hours were assigned at random to induction with oxytocin or to expectant management for 48 hours followed by induction if necessary. Of 168 eligible women, 123 (73%) agreed to participate. More women in the induction group (23%) than in the expectant group (10%) had operative delivery, either cesarean section or instrumental vaginal delivery. In the induction group 41% received analgesia versus 24% in the expectant group (p < 0.005). There was no difference in the rate of maternal and neonatal infection between groups and sepsis was not observed. The active policy of oxytocin induction exposed the mother to a higher risk of operative delivery and a less comfortable labor than the 48 hours expectant care option.", "The rate of Cesarean Section for failed induction of labor and maternal and fetal compilations are high when labor is induced in a nulliparas women with an unripe cervix by amniotomy and oxytocin infusion. Prostaglandins (PG) in different forms have been used for ripening the cervix with an aim of reducing these problems. A prospective randomized trial was performed on one hundred primigravid women between 37 and 42 weeks of gestation with singleton pregnancy, cephalic presentation and unfavorable cervix (Modified Bishop Score < or = 5) in the department of Obstetrics & Gynaecology of Institute of Postgraduate Medicine & Research from 1st May 1996 to 30th April 1997. In this study the efficiency of prostaglandin E2 intracervical (PGE2 IC) gel in induction of labor in a group of primigravid women with unripe cervix was assessed and compared with another group with similar characteristics using oxytocin infusion and artificial rupture of membrane (ARM). The Modified Bishop Score (MBS), interval between IOL and onset of labor and the duration of labor after insertion of PGE2 gel was significantly different from those of oxytocin infusion group. But the Apgar Score at 1 & 5 min had shown no statistically significant difference. Any significant difference could also not be detected in the mode of delivery between the two induction group. The proportion of emergency Cesarean Section (CS) was high in the oxytocin infusion group than that of in the prostaglandin group. There was also no significant difference regarding the acceptability of both the induction methods.", "To test the hypothesis that commencing induction of labor in the morning more closely reflects the physiologic timing of onset of labor and is associated with fewer women who remain undelivered 24 hours after cervical ripening and induction begins.\n This was a nested randomized clinical trial, conducted between April 2001 and December 2004. Pregnant women at more than 36+6 weeks gestation with a cephalic presentation who were scheduled for prostaglandin induction of labor were eligible to participate. Women were randomly assigned to either admission in the morning (0800 hours) or admission in the evening (2,000 hours). The primary outcome measures were vaginal birth not achieved in 24 hours, uterine hyperstimulation with associated fetal heart rate changes, and cesarean delivery.\n A total of 620 women were entered in the trial, with 280 women in the morning admission group and 340 women in the evening admission group. There were no statistically significant differences between the timing of admission for induction and the primary trial outcomes. However, women admitted in the morning were less likely to require oxytocin infusion (morning admission 126 of 280 [45.0%] compared with evening admission 184 of 340 [54.1%]; relative risk 0.83, 95% confidence interval 0.70-0.97; P=.022). Nulliparous women admitted in the morning were less likely to require operative vaginal birth (morning admission 10 of 62 [16.1%] compared with evening admission 28 of 82 [34.2%]; relative risk 0.47, 95% confidence interval 0.25-0.90; P=.015).\n For women who require induction of labor, consideration should be given to admission in the morning rather than admission in the evening.\n Australian Clinical Trials Registry, www.actr.org.au, 12606000156583.", "In a randomized controlled study of 100 women of low parity and favourable induction features, induction of labour by means of a single vaginal tablet containing 3 mg of prostaglandin E2 (PGE2) was compared with the conventional method of amniotomy and intravenous oxytocin. Four of the patients (8%) who received the prostaglandin tablet required additional intravenous oxytocin to achieve delivery. The prostaglandin group had a longer mean overall induction-delivery interval but a shorter amniotomy-delivery interval than the oxytocin group. One patient in the PGE2 group and two in the oxytocin group required caesarean section. The PGE2 treated patients expressed a higher level of satisfaction with their method of induction, they required less analgesia, had less blood loss at delivery and their babies had a lower incidence of neonatal jaundice." ]

[ "9512207", "2052460", "2181103", "17485450", "1403397", "8120721", "9846921", "10867849", "2651597" ]

[ "Randomized, controlled, blinded trial of doxapram for extubation of the very low birthweight infant.", "[A comparison of the efficacy of aminophylline and doxapram in preventing idiopathic apnea in preterm newborn infants].", "A blinded, randomized, placebo-controlled trial to compare theophylline and doxapram for the treatment of apnea of prematurity.", "Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: a randomized, controlled trial.", "Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema.", "Randomized, controlled trial of nasopharyngeal continuous positive airway pressure in the extubation of very low birth weight infants.", "Low-dose doxapram for treatment of apnoea following early weaning in very low birthweight infants: a randomized, double-blind study.", "Elective use of nasal continuous positive airways pressure following extubation of preterm infants.", "Successful extubation of newborn infants without preextubation trial of continuous positive airway pressure." ]

[ "The objective of the study was to determine whether administering doxapram by infusion to the very low birthweight infant, prior to extubation during the first 3 weeks of life, would increase the incidence of successful extubation. The study patients, 56 infants of less than 1251 g birthweight and less than 30 weeks' gestation, were entered in the first 3 weeks of life when lung disease had started to improve. A randomized blinded trial was performed, with infants receiving 3.5 mg kg(-1) doxapram bolus, followed by an infusion at 1 mg kg(-1) h(-1), or placebo. Weaning from positive pressure ventilation was standardized and extubation occurred after a 12 h trial of an intermittent mandatory ventilation (IMV) rate of 6 breaths min(-1), if PCO2 < 55 mmHg, pH > 7.26, and FiO2 < 0.45. Study drug was continued for 48 h postextubation, and the infants were placed on nasopharyngeal continuous positive airway pressure (CPAP) for 72 h postextubation. Extubation failure within the first 72 h after extubation was objectively defined in terms of acidosis (pH < 7.26), hypercarbia (PCO2 > 55 mmHg), excessive oxygen requirement (FiO2 > 0.8) or frequent apnoea (more than three in 12 h, or more than two requiring face mask IMV in 24 h). No difference was noted in the frequency of successful extubation between the groups. Fifteen infants in each group were successfully extubated before the 10th day of the study. In conclusion, when given in accordance with this protocol doxapram does not increase the likelihood of successful extubation in the very low birthweight infant. Increasing successful extubations in this group of infants will require other strategies.", "Doxapram is an analeptic of the respiratory system that has been used in the last few years for the treatment of idiopathic apnea spells in infants who show resistance to methylxantine. In this study we have compared the efficacy of aminophylline and doxapram for the prevention of idiopathic apnea spells in two groups of preterm infants comparable for gestational age, birthweight and postnatal age. The two drugs resulted to be effective in preventing the spells of apnea in 66% and 60% of the cases respectively. In the cases in which there was a partial or negative response, the association of the two substances resulted in a noticeable reduction of the apnea spells. The positive effect of the association of aminophylline and doxapram is probably due to the different action mechanism on the stimulation of the respiratory system.", "A blinded, randomized, placebo-controlled trial was conducted to evaluate the effectiveness of theophylline and doxapram therapy in 31 infants with significant apnea of prematurity. Of 10 infants, two had a short-term response to placebo, 8 of 10 infants to theophylline, and 7 of 11 infants to doxapram (placebo vs treatment with theophylline or doxapram: p = 0.01). The two infants who initially responded to placebo remained responsive for the duration of the study. Of the eight infants in whom treatment with placebo failed, five were randomly assigned to receive theophylline, for a total of 15 infants treated with theophylline, and two of the eight were randomly assigned to receive doxapram, for a total of 13 infants treated with doxapram; the remaining infant required tracheal intubation. Of the 15 infants randomly assigned to receive theophylline, seven responded for the duration of the study; of the eight infants who did not respond to treatment with theophylline, five responded to doxapram, one responded to a combination of theophylline and doxapram, and two remained resistant to treatment. Of the 13 infants randomly assigned to receive doxapram four responded for the duration of the study; of the nine who did not respond to doxapram, seven responded to theophylline, one responded to a combination of theophylline and doxapram, and one remained resistant to treatment. This study demonstrates that although therapy with theophylline or doxapram is associated with a significant short-term reduction in the incidence of apnea compared with that in placebo-treated infants, the long-term response to treatment is frequently incomplete and is not sustained more than 1 week.", "The purpose of this work was to compare the efficacy of propofol, a hypnotic agent, to the regimen of morphine, atropine, and suxamethonium as an induction agent for nonemergency neonatal endotracheal intubation. We hypothesized that propofol aids intubation by allowing the continuation of spontaneous breathing.\n We conducted a randomized, open-label, controlled trial of infants who required nonemergency endotracheal intubation. Primary outcome was successful intubation confirmed by chest auscultation and clinical examination of the infant.\n Infants randomly assigned to propofol (n = 33) and the morphine, atropine, and suxamethonium regimen (n = 30) were comparable in median gestational age (27 vs 28 weeks), birth weight (1020 vs 1095 g), weight at intubation (1068 vs 1275 g), and age at intubation (4 vs 3 days). Sleep or muscle relaxation were achieved within 60 seconds in both groups, but time to achieve successful intubation was more than twice as fast with propofol (120 vs 260 seconds). Blood pressure and heart rates were not different, but intraprocedural oxygen saturations were significantly lower in infants on the morphine, atropine, and suxamethonium regimen (trough arterial oxygen saturation: 60% vs 80%). Nasal/oral trauma was less common, and recovery time was shorter (780 vs 1425 seconds) in the propofol group. No significant adverse effects were seen in either group.\n Propofol is more effective than the morphine, atropine, and suxamethonium regimen as an induction agent to facilitate neonatal nasal endotracheal intubation. Importantly, hypoxemia was less severe, probably because of the maintenance of spontaneous breathing. A controlled environment may have promoted the ease of intubation, resulting in less trauma. The shorter duration of action would be advantageous in a compromised infant.", "We studied 50 preterm infants who had multiple or traumatic endotracheal intubations, or whose duration of endotracheal intubation was > or = to 14 days, and who were considered at high risk for airway edema. These infants were enrolled in a prospective, randomized, controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress. At study entry, both groups had similar weights, postnatal ages, methylxanthine use, ventilator settings, blood gas values, and pulmonary function test results (dynamic compliance, total respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure, minute ventilation, and peak inspiratory and expiratory flow rates). Patients underwent blood gas studies, physical examinations, and pulmonary function testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to 24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25 mg/kg per dose, at baseline, and then every 8 hours for a total of three doses; 23 infants received saline solution at corresponding times. Eighteen to twenty-four hours after extubation, total pulmonary resistance increased by 225% from baseline in the control group compared with 33% in the dexamethasone group (p < 0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants, 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients (p < 0.006). Of the 23 control patients, 4 required reintubation compared with none of the treated group (p < 0.05). We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight, high-risk preterm infants.", "We conducted a prospective, randomized controlled trial to determine whether extubation of very low birth weight infants was facilitated by the use of nasopharyngeal continuous positive airway pressure (CPAP). Eligible infants included patients weighing 600 to 1500 gm at birth who required tracheal intubation within 48 hours of birth and who met specific predetermined criteria for extubation by day 14 of life. We also sought to determine whether varying the duration of nasopharyngeal CPAP influenced the likelihood of successful extubation. Infants underwent random assignment to receive nasopharyngeal CPAP until resolution of lung disease (n = 40), 6 hours of nasopharyngeal CPAP (n = 42), or oxygen supplementation delivered by hood (n = 42). Extubation failure was predefined as a requirement for > or = 80% oxygen, pH < or = 7.20, severe apnea, or predefined clinical deterioration, and extubation success was predefined as the ability to remain free of a requirement for mechanical ventilation for 7 days and a 66% reduction in the need for supplemental oxygen. Each group was similar with regard to race, sex, and birth weight. Extubation was successful in 62%, 61%, and 60% of infants. After stratification by birth weight, there were no significant differences in the rates of successful extubation among the treatment groups. We conclude that nasopharyngeal CPAP does not improve the likelihood of successful extubation of very low birth weight infants who are ready for extubation within the first 2 weeks of life.", "The effects of low-dose doxapram (0.5 mg kg(-1)h(-1)) in combination with caffeine were evaluated on apnoea frequency following weaning from mechanical ventilation, and on blood pressure, in very low birthweight (BW) premature infants. Twenty-nine infants with BW < or=1250 g, gestational age at birth (GA) <34 weeks and postnatal age <5 d, who required minimal respiratory support, were included. Following randomization, they received a loading dose of caffeine citrate and a continuous infusion of doxapram (doxapram, n=14) or placebo (n=15) was started. They were extubated 8 h after starting the infusion, which was continued for 5 d. During this period, weaning was well tolerated in both groups, apnoeas occurred less frequently and there was a greater increase in systolic blood pressure in infants treated with doxapram than in controls. Plasma doxapram levels were also higher than expected. It is therefore suggested that doxapram, even at low doses, should not be used during the first few days of life. Careful monitoring of blood pressure is required if doxapram is used later.", "The aim of this study was to determine whether elective use of nasal continuous positive airways pressure (CPAP) following extubation of preterm infants was well tolerated and improved short- and long-term outcomes. A randomized comparison of nasal CPAP to headbox oxygen was undertaken and a meta-analysis performed including similar randomized trials involving premature infants less than 28 days of age. A total of 150 infants (median gestational age 30 weeks, range 24-34 weeks) were randomized in two centres. Fifteen nasal CPAP infants and 25 headbox infants required increased respiratory support post-extubation and 15 nasal CPAP infants and nine headbox infants required reintubation (non significant). Eight infants became intolerant of CPAP and were changed to headbox oxygen within 48 h of extubation; 19 headbox infants developed apnoeas and respiratory acidosis requiring rescue nasal CPAP, 3 ultimately were re-intubated. Seven other trials were identified, giving a total number of 569 infants. Overall, nasal CPAP significantly reduced the need for increased respiratory support (relative risk, 0.57, 95% CI 0.43-0.73), but not for re-intubation (relative risk 0.89, 95% CI 0.68-1.17). Nasal CPAP neither influenced significantly the intraventricular haemorrhage rate reported in four studies (relative risk 1.0, 95% CI 0.55, 1.82) nor that of oxygen dependency at 28 days reported in six studies (relative risk 1.0, 95% CI 0.8, 1.25). In two studies nasal CPAP had to be discontinued in 10% of infants either because of intolerance or hyperoxia.\n Elective use of nasal continuous positive airways pressure post-extubation is not universally tolerated, but does reduce the need for additional support.", "Sixty newborn infants who had been mechanically ventilated through 3.0- or 3.5-mm endotracheal tubes were studied to examine the necessity of a preextubation trial of continuous positive airway pressure (CPAP). Thirty randomly assigned study infants were directly extubated from intermittent mandatory ventilation rates of six per minute; 30 randomly assigned control infants were extubated after a six-hour trial of continuous positive airway pressure of 3 cm H2O. Changes in respiratory rate, in PCO2, and in PO2/FIO2 were similar. All 30 study infants tolerated direct extubation without significant apnea or respiratory acidosis. Two study and eight control infants developed apnea during six hours after intermittent mandatory ventilation was discontinued (chi 2 = 4.3, P less than .05). Five control and no study infants had apneic episodes greater than or equal to 0.5 per hour (chi 2 = 5.5, P less than .02). The results of this study suggest that newborn infants may tolerate direct extubation from low intermittent mandatory ventilation rates without a preextubation trial of CPAP. A preextubation trial of CPAP appears to be unnecessary and may cause more frequent apnea in newborn infants if used for more than several hours." ]

[ "19543080", "19433778", "490882", "17635851", "19142758", "16147905", "16148616", "12874091", "12517683" ]

[ "Reduction of morning blood pressure surge after treatment with nifedipine GITS at bedtime, but not upon awakening, in essential hypertension.", "Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: improved blood pressure control with bedtime dosing.", "Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group.", "Comparison of the efficacy of morning versus evening administration of telmisartan in essential hypertension.", "Administration-time-dependent effects of olmesartan on the ambulatory blood pressure of essential hypertension patients.", "Administration time-dependent effects of valsartan on ambulatory blood pressure in elderly hypertensive subjects.", "Treatment of non-dipper hypertension with bedtime administration of valsartan.", "Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects.", "Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension." ]

[ "The extent of morning blood pressure (BP) surge upon wakening has been associated with increased incidence of stroke and cardiovascular mortality. This trial investigated the antihypertensive efficacy and effects on the morning BP surge of awakening versus bedtime administration of nifedipine in essential hypertension.\n We studied 238 previously untreated hypertensive patients (108 men and 130 women), 53.3+/-11.4 years of age, randomly assigned to receive nifedipine (30 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured for 48 h before and after 8 weeks of treatment.\n The BP reduction after the treatment was significantly greater with bedtime dosing (P<0.001). The proportion of patients with controlled ambulatory BP thus increased from 28 to 43% (P = 0.019) with bedtime treatment. The sleep time relative BP decline was unchanged after morning treatment, but increased toward a more dipping pattern after bedtime dosing (P = 0.026 between groups). The morning BP surge was unchanged after the administration of nifedipine upon awakening (1.4/1.2 mmHg reduction in systolic/diastolic BP surge, P>0.270), but significantly reduced after bedtime dosing (6.2/4.4 mmHg reduction, P<0.001).\n Nifedipine efficiently reduces BP for the entire 24 h and to a significantly larger extent after bedtime administration. The significant added efficacy on reducing night-time BP, the decrease in the prevalence of a nondipper BP pattern, and the significant decrease in morning BP surge (all relevant markers of cardiovascular morbidity and mortality) of bedtime as compared with morning administration, consistently indicate that nifedipine should preferably be administered at bedtime in patients with essential hypertension.", "Clinical studies have demonstrated a different effect on blood pressure of some angiotensin-converting enzyme inhibitors when administered in the morning versus the evening. Their administration at bedtime resulted in a higher effect on nighttime blood pressure as compared with morning dosing. This study investigated the administration time-dependent effects of ramipril on ambulatory blood pressure. We studied 115 untreated hypertensive patients, 46.7+/-11.2 years of age, randomly assigned to receive ramipril (5 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured for 48 hours before and after 6 weeks of treatment. The blood pressure reduction during diurnal activity was similar for both treatment times. Bedtime administration of ramipril, however, was significantly more efficient than morning administration in reducing asleep blood pressure. The awake:asleep blood pressure ratio was decreased after ramipril on awakening but significantly increased toward a more dipping pattern after bedtime dosing. The proportion of patients with controlled ambulatory blood pressure increased from 43% to 65% (P=0.019) with bedtime treatment. Nocturnal blood pressure regulation is significantly better achieved at bedtime as compared with morning administration of ramipril, without any loss in efficacy during diurnal active hours. This might be clinically important, because nighttime blood pressure has been shown to be a more relevant marker of cardiovascular risk than diurnal mean values. The change in the dose-response curve, increased proportion of controlled patients, and improved efficacy on nighttime blood pressure with administration of ramipril at bedtime should be taken into account when prescribing this angiotensin-converting enzyme inhibitor for treatment of essential hypertension.", "The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with \"mild\" hypertension.", "Valsartan administration at bedtime as opposed to on wakening improves the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Yet to be determined is whether this administration time-dependent efficacy is a class-related feature, characteristic of all angiotensin receptor blockers or specific only to valsartan. Terminal half-life is a major difference between angiotensin receptor blockers, being largest ( approximately 24 hours) for telmisartan. This trial investigated the administration time-dependent antihypertensive efficacy of telmisartan. We studied 215 patients with hypertension (114 men and 101 women), 46.4+/-12.0 years of age, randomly assigned to receive telmisartan (80 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured for 48 hours before and after 12 weeks of treatment. The significant blood pressure reduction after treatment was similar for both groups. Bedtime administration of telmisartan, however, was more efficient than morning dosing in reducing the nocturnal blood pressure mean. The sleep time-relative blood pressure decline was slightly reduced after telmisartan on awakening but significantly increased with bedtime dosing, thus reducing the prevalence of nondipping from baseline by 76%. Telmisartan administered at bedtime, as opposed to morning dosing, improved the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Nocturnal BP regulation is significantly better achieved with bedtime dosing of telmisartan. Results from this prospective trial suggest that these beneficial features of bedtime dosing may be class related for angiotensin receptor blockers. These results should be taken into account when prescribing this class of antihypertensive medication for treatment of essential hypertension.", "Previous studies established that a single daily dose of olmesartan remains effective for the entire 24 h without alteration of the day-night blood pressure (BP) pattern. On the other hand, the administration of valsartan or telmisartan at bedtime, as opposed to upon wakening, improves the sleep-time relative BP decline toward a greater dipper pattern without loss of 24 h efficacy. Yet to be determined is whether this administration-time-dependent efficacy is a class-related feature, characteristic of all angiotensin-receptor-blocker (ARB) medications. We studied 123 grade 1 and 2 hypertensive patients, 46.6+/-12.3 yrs of age, randomly assigned to receive olmesartan (20 mg/day) as a monotherapy either upon awakening or at bedtime for three months. BP was measured by ambulatory monitoring for 48 consecutive hours before and after treatment. The 24 h BP reduction was similar for both treatment times. Administration of olmesartan at bedtime, however, was significantly more efficient than morning administration in reducing the nocturnal BP mean. The sleep-time relative BP decline was slightly reduced with olmesartan ingestion upon awakening but significantly increased with ingestion at bedtime, thus reducing the prevalence of non-dipping from baseline by 48%. Olmesartan administration at bedtime, as opposed to in the morning, improved the awake/asleep BP ratio toward a greater dipper pattern without loss of 24 h efficacy. Nocturnal BP regulation was significantly better achieved with bedtime as compared to morning dosing of olmesartan. These effects are comparable to those previously reported for valsartan and telmisartan, thus suggesting that they may be class-related features of ARB medications in spite of differences in their half-life kinetics. These administration-time-dependent effects should be taken into account when prescribing ARB medications for treatment of essential hypertension.", "Previous results have indicated that valsartan administration at bed-time, as opposed to upon wakening, improves the diurnal/nocturnal ratio of blood pressure (BP) toward a normal dipping pattern, without loss of 24 h efficacy. This ratio is characterized by a progressive decrease with aging. Accordingly, we investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin blocking agent, in elderly hypertensive patients. We studied 100 elderly patients with grade 1-2 essential hypertension (34 men and 66 women), 68.2+/-4.9 years of age, randomly assigned to receive valsartan (160 mg/d) as a monotherapy either upon awakening or at bed-time. BP was measured for 48 h by ambulatory monitoring, at 20 min intervals between 07:00 to 23:00 h and at 30 min intervals at night, before and after 3 months of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately determine the duration of sleep and wake spans to enable the accurate calculation of the diurnal and nocturnal means of BP for each subject. There was a highly significant BP reduction after 3 months of valsartan treatment (p < 0.001). The reduction was slightly larger with bed-time dosing (15.3 and 9.2 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively) than with morning dosing (12.3 and 6.3 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively). The diurnal/nocturnal ratio, measured as the nocturnal decline of BP relative to the diurnal mean, was unchanged in the group ingesting valsartan upon awakening (-1.0 and -0.3 for systolic and diastolic BP; p > 0.195). This ratio was significantly increased (6.6 and 5.4 for systolic and diastolic BP; p < 0.001) when valsartan was ingested at bed-time. The reduction of the nocturnal mean was doubled in the group ingesting valsartan at bed-time, as compared to the group ingesting it in the morning (p < 0.001). In elderly hypertensive patients, mainly characterized by a diminished nocturnal decline in BP, bed-time valsartan dosing is better than morning dosing since it improves efficacy during the nighttime sleep span, with the potential reduction in cardiovascular risk that has been associated with a normalized diurnal/nocturnal BP ratio.", "Previous results have indicated that valsartan administration at bedtime, as opposed to upon wakening, may improve the diurnal: nocturnal ratio of blood pressure without loss in 24-h coverage and efficacy.\n To investigate the administration time-dependent antihypertensive efficacy of valsartan in non-dipper patients.\n We studied 148 non-dipper patients with grade 1-2 essential hypertension, aged 53.0+/-12.6 years, who were randomly assigned to receive valsartan (160 mg/day) as a monotherapy either on awakening or at bedtime. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per subject basis.\n The significant blood pressure reduction after 3 months of valsartan (P<0.001) was similar for both treatment times (13.1 and 8.5 mmHg reduction in the 24-h mean of systolic and diastolic blood pressure with morning administration; 14.7 and 10.3 mmHg with bedtime administration; P>0.126 for treatment-time effect). The diurnal: nocturnal ratio of blood pressure was significantly increased only when valsartan was administered before bedtime, which resulted in 75% of the patients in this group reverting to dippers, a significant increase in the percentage of patients with controlled blood pressure over 24 h, and a reduction in urinary albumin excretion.\n In non-dipper hypertensive patients, dosing time with valsartan should be chosen at bedtime, for improved efficacy during the nocturnal resting hours, as well as the potential associated reduction in cardiovascular risk.", "This study investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin II receptor blocker. We studied 90 subjects (30 men and 60 women), 49.0+/-14.3 (mean+/-SD) years of age with stage 1 to 2 essential hypertension; they were randomly assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The highly significant blood pressure reduction after 3 months of treatment with valsartan (P<0.001) was similar for both treatment times (17.0 and 11.3 mm Hg reduction in the 24-hour mean of systolic and diastolic blood pressure with morning administration and 14.6 and 11.4 mm Hg reduction with bedtime administration; P>0.174 for treatment time effect). Valsartan administration at bedtime as opposed to on wakening resulted in a highly significant average increase by 6% (P<0.001) in the diurnal-nocturnal ratio of blood pressure; this corresponded to a 73% relative reduction in the number of nondipper patients. The findings confirm that valsartan efficiently reduces blood pressure throughout the entire 24 hours, independent of treatment time. They also suggest that time of treatment can be chosen according to the dipper status of a patient to optimize the effect of antihypertensive therapy, an issue that deserves further investigation.", "The efficacy and safety of a chronotherapeutic, graded-release diltiazem HCl extended-release (GRD) 120-, 240-, 360- and 540-mg dose administered once-daily at bedtime (10 PM) were evaluated in a 7-week randomized, double-blind comparison to placebo and to GRD 360 mg administered once-daily at 8 AM in 478 patients with moderate-to-severe essential hypertension.\n We assessed the change from baseline to end point in trough diastolic blood pressure (DBP) at 6 PM to 10 PM and in mean DBP from 6 AM to 12 noon between GRD 360 mg PM and GRD 360 mg AM, measured by ambulatory BP monitoring (ABPM).\n Bedtime doses of GRD showed dose-related mean reductions in trough DBP that were significant for GRD doses of 240 mg and higher. Bedtime GRD 360 mg was associated with a significantly greater reduction in mean DBP between 6 AM and 12 noon compared to morning GRD 360 mg with a least squares mean for treatment difference of -3.3 mm Hg (P =.0004). Similar dose-related and significant reductions in systolic BP (SBP) and heart rate (HR) were obtained. Incidence of adverse events (AEs) for all GRD groups (44.5%) was less than that obtained for the placebo group (49.3%). The 540-mg group showed an incidence of AEs (43.5%) similar to that observed for the 240-mg group (42.6%).\n The GRD dose-dependently significantly reduces BP and HR over the 24-h interval after once-daily bedtime dosing. Further greater reductions were obtained between 6 AM and 12 noon, when circadian BP is highest, compared to morning administration of the same dose. The 540-mg GRD was safe, well tolerated, and offers further therapeutic option for patients with severe hypertension who required additional BP control." ]

[ "10326778", "1944900", "18568115", "19392908", "16501756", "20004065", "2178869", "2082953", "17632223" ]

[ "Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease.", "Long-term acetyl-L-carnitine treatment in Alzheimer's disease.", "Extended use of nicotine replacement therapy to maintain smoking cessation in persons with schizophrenia.", "Extended treatment of older cigarette smokers.", "[Randomized clinical trial: effectiveness of the cognitive-behavioral approach and the use of nicotine replacement transdermal patches for smoking cessation among adults in Rio de Janeiro, Brazil].", "Nicotine patch vs. nicotine lozenge for smoking cessation: an effectiveness trial coordinated by the Community Clinical Oncology Program.", "Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia.", "Lack of efficacy of hydergine in patients with Alzheimer's disease.", "A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia." ]

[ "Acute nicotine injections have been found to improve attentional performance in patients with Alzheimer's disease (AD), but little is known about chronic nicotine effects.\n The present study was undertaken to evaluate the clinical and neuropsychological effects of chronic transdermal nicotine in Alzheimer's disease subjects over a 4-week period.\n The double-blind, placebo controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period. Patients wore the nicotine patch (Nicotrol) for 16 h a day at the following doses: 5 mg/day during week 1, 10 mg/day during weeks 2 and 3 and 5 mg/day during week 4. The eight subjects had mild to moderate AD and were otherwise healthy.\n Nicotine significantly improved attentional performance as measured by the Conners' continuous performance test (CPT). There was a significant reduction in errors of omission on the CPT which continued throughout the period of chronic nicotine administration. The variability of hit reaction time (reaction time for correct responses) on the CPT was also significantly reduced by chronic nicotine. Nicotine did not improve performance on other tests measuring motor and memory function.\n The sustained improvement in attention found in this study with nicotine dermal patches is encouraging. However, the lack of detected effects of nicotine treatment on other cognitive and behavioral domains in this study leaves questions concerning the clinical impact of nicotinic treatment in Alzheimer's disease. The modest size of this study limited statistical power which may have been needed to detect more subtle but clinically significant cognitive effects. Higher doses of nicotine, other nicotinic ligands or combination treatment of nicotine with other therapies may be efficacious for producing broader therapeutic effects.", "In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.", "This study was designed to determine the feasibility and efficacy of long-term nicotine replacement therapy (NRT) in helping persons with schizophrenia remain tobacco-free. Fifty smokers with a diagnosis of schizophrenia or schizo-affective disorder and whose symptoms had been stable for at least two months were enrolled in a program providing group support and NRT (patches) in individually adjusted doses set to maintain baseline nicotine intake. All participants attended weekly group support/motivation sessions. Smoking activity was determined by measuring carbon monoxide levels in expired air. Participants who quit tobacco use completely during the first three months were entered into a single-blind phase in which they received either placebo or active nicotine patches for up to six additional months, along with biweekly group sessions. Sixty days into the open-label phase, 66% of the subjects had reduced their use of tobacco by at least 75%. After 90 days of open-label treatment, 18 subjects (36%) were tobacco-free and qualified to enter the six-month, single-blind phase, eight on placebo and nine on active patches. A significantly greater proportion of those on placebo (8 of 8) compared with those on active patches (3 of 9) relapsed prior to completion of the 6-month period. This difference is statistically significant at the p = 0.009 level. The results of this study indicate that long-term use of NRT is feasible and effective for sustained tobacco-free success and may be an important strategy for reducing health risks due to tobacco use in this special population.", "Tobacco dependence treatments achieve abstinence rates of 25-30% at 1 year. Low rates may reflect failure to conceptualize tobacco dependence as a chronic disorder. The aims of the present study were to determine the efficacy of extended cognitive behavioral and pharmacological interventions in smokers > or = 50 years of age, and to determine if gender differences in efficacy existed.\n Open randomized clinical trial.\n A free-standing, smoking treatment research clinic.\n A total of 402 smokers of > or = 10 cigarettes per day, all 50 years of age or older.\n Participants completed a 12-week treatment that included group counseling, nicotine replacement therapy (NRT) and bupropion. Participants, independent of smoking status, were then assigned randomly to follow-up conditions: (i) standard treatment (ST; no further treatment); (ii) extended NRT (E-NRT; 40 weeks of nicotine gum availability); (iii) extended cognitive behavioral therapy (E-CBT; 11 cognitive behavioral sessions over a 40-week period); or (iv) E-CBT plus E-NRT (E-combined; 11 cognitive behavioral sessions plus 40 weeks nicotine gum availability).\n Primary outcome variable was 7-day point prevalence cigarette abstinence verified biochemically at weeks 24, 52, 64 and 104.\n The most clinically important findings were significant main effects for treatment condition, time and the treatment x time interaction. The E-CBT condition produced high cigarette abstinence rates that were maintained throughout the 2-year study period [(week 24 (58%), 52 (55%), 64 (55%) and 104 (55%)], and was significantly more effective than E-NRT and ST across that period. No other treatment condition was significantly different to ST. No effects for gender were found.\n Extended cognitive behavioral treatments can produce high and stable cigarette abstinence rates for both men and women. NRT does not add to the efficacy of extended CBT, and may hamper its efficacy. Research is needed to determine if these results can be replicated in a sample with a greater range of ages, and improved upon with the addition of medications other than NRT.", "Randomized clinical trial carried out to investigate the effectiveness of the cognitive-behavioral approach and nicotine replacement therapy with nicotine patches for smoking cessation. Participated 1,199 adults, volunteers, in Rio de Janeiro, Brazil, randomly assigned to 10 different groups: intensive brief counseling group (GB), with 1 or 2 sessions (G1-G2), and with 3 or 4 sessions (G3-G4), with/without nicotine replacement therapy (NRT). Abstinence proportions were estimated during 12 months. These proportions among participants not assigned to NRT were 20% (GB), 17% (G1-G2), and 23% (G3-G4); and among assigned NRT groups were 30% (GBA), 34% (G1A-G2A), and 33% (G3A-G4A). After multiple adjustments, the abstinence proportions ratios seemed to follow a \"dose-response\" pattern: compared to GB, the ratios were 0.85 (G1-G2), 1.13 (G3-G4), 1.51 (GBA), 1.66 (G1A-G2A), and 1.75 (G3A-G4A). The results suggest that use of NRT increases the abstinence proportion for cessation. The \"dose-response\" pattern suggests that cognitive-behavioral could be the reasonable option in the smoking cessation therapy.", "Nicotine replacement therapies are efficacious for treating nicotine dependence. However, limited data exist on benefits of different NRTs and predictors of treatment outcome. This study compared the effectiveness of transdermal nicotine vs. nicotine lozenge for smoking cessation and identified predictors of treatment response.\n A randomized, open-label effectiveness trial was conducted at 12 medical sites participating in the National Cancer Institute's Community Clinical Oncology Program. The sample consisted of 642 treatment-seeking smokers randomized to 12 weeks of transdermal nicotine or nicotine lozenge.\n Smoker characteristics were assessed at baseline, and 24-h point prevalence abstinence confirmed with breath carbon monoxide (CO) was evaluated at end of treatment (EOT) and at a 6-month follow-up. There was a trend for higher quit rates for transdermal nicotine vs. nicotine lozenge at EOT (24.3% vs. 18.7%, p=.10) and 6 months (15.6% vs. 10.9%, p=.10). A logistic regression model of EOT quit rates showed smokers who preferred transdermal nicotine, were not reactive to smoking cues, and did not use nicotine to alleviate distress or stimulate cognitive function had higher quit rates on transdermal nicotine. A logistic regression model of 6-month quit rates showed smokers who preferred transdermal nicotine had higher quit rates on transdermal nicotine, and smokers who used nicotine to alleviate distress or stimulate cognitive processes had lower quit rates on nicotine lozenge.\n Transdermal nicotine may be more effective than nicotine lozenge for smokers who prefer transdermal nicotine and do not smoke to alleviate emotional distress or stimulate cognitive function.\n Copyright 2009 Elsevier Ireland Ltd. All rights reserved.", "A randomized, double-blind, placebo-controlled, parallel-group clinical trial was carried out to compare 24-week periods of treatment with 1 g acetyl-l-carnitine twice daily and placebo in the treatment of patients with dementia of the Alzheimer type. A total of 36 patients entered the trial, of whom 20 patients (7 active, 13 placebo) completed the full 24 weeks. Whilst several of the efficacy indices showed little change in either group during the trial, there was an apparent trend for more improvement in the acetyl-l-carnitine group in relation to the Names Learning Test and a computerized Digit Recall Test, both related to aspects of short-term memory. Similarly, there was a trend for reaction time in the computerized classification test to show less deterioration in the active treatment group. Changes within groups, and changes between groups, failed to reach statistical significance, at least partially because of the small number of patients available for analysis. Two indices of overall therapeutic benefit showed a trend for less deterioration in the active-treatment group than in the placebo group. Nausea and/or vomiting occurred in 5 patients in the acetyl-l-carnitine group. Laboratory tests revealed no signs of drug toxicity. The results suggest that acetyl-l-carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia, particularly those related to short-term memory.", "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.", "The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention." ]

[ "3351998", "1592640", "20360500", "12142826", "11514765", "16721238", "17049347", "12579017", "11514766" ]

[ "A comparison of nail-plate fixation and Ender's nailing in pertrochanteric fractures.", "[The gamma-nail as a resilient alternative to the dynamic hip screw in unstable proximal femoral fractures in the elderly].", "A comparison of the long gamma nail with the sliding hip screw for the treatment of AO/OTA 31-A2 fractures of the proximal part of the femur: a prospective randomized trial.", "Pertrochanteric fractures: is there an advantage to an intramedullary nail?: a randomized, prospective study of 206 patients comparing the dynamic hip screw and proximal femoral nail.", "Prospective randomized controlled trial of an intramedullary nail versus dynamic screw and plate for intertrochanteric fractures of the femur.", "Cephalomedullary nails in the treatment of high-energy proximal femur fractures in young patients: a prospective, randomized comparison of trochanteric versus piriformis fossa entry portal.", "One and two femoral neck screws with intramedullary nails for unstable trochanteric fractures of femur in the elderly--randomised clinical trial.", "Slotted intramedullary hip screw nails reduce proximal mechanical unloading.", "Prospective randomized comparison between a dynamic hip screw and a mini-invasive static nail in fractures of the trochanteric area: preliminary results." ]

[ "A randomized comparison was made of condylocephalic (Ender) nails and a nail-plate technique (McLaughlin) for fixation of trochanteric fractures, to evaluate the consumption of acute hospital bed-days, number of reoperations, peroperative blood loss, and operation time. Reoperations were performed in 30% of the Ender group and in 10% of the McLaughlin group and blood loss was doubled for the McLaughlin method. Our study has shown, that in our hands, patients operated on with Ender nails had more reoperations, but in spite of this the total cost, in the form of days in hospital or operation time was not increased.", "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.", "Controversy exists with regard to whether to treat AO/OTA 31-A2 fractures of the proximal part of the femur with an intramedullary device or an extramedullary device. A prospective, randomized, controlled trial was performed to compare the outcome of treatment of these unstable fractures of the proximal part of the femur with either a sliding hip screw or a long gamma nail.\n Two hundred and ten patients presenting with an AO/OTA 31-A2 fracture of the proximal part of the femur were randomized, at the time of admission, to fixation with use of either a long gamma nail or a sliding hip screw. The primary outcome measure was reoperation within the first postoperative year. Secondary measures included mortality, length of hospital stay, transfusion rate, change in mobility and residence, and quality of life as measured with the EuroQol 5D outcome score.\n There was no significant difference between the reoperation rates for the two groups. In total, five patients (three from the long-gamma-nail group and two from the sliding-hip-screw group) underwent revision surgery because of cut-out. Tip-apex distance was found to correlate with the implant cut-out rate. There was no significant difference between the two groups in terms of the EuroQol 5D outcome scores, the mortality rates after correction for the mini-mental score, or any of the secondary outcome measures.\n When compared with the long gamma nail, the sliding hip screw should remain the gold standard for the treatment of AO/OTA 31-A2 fractures of the proximal part of the femur because it is associated with similar outcomes with less expense.", "To compare the results between a sliding compression hip screw and an intramedullary nail in the treatment of pertrochanteric fractures.\n Prospective computer-generated randomization of 206 patients into two study groups: those treated by sliding compression hip screw (Group 1; n = 106) and those treated by intramedullary nailing (Group 2; n = 100).\n University Level I trauma center.\n All patients over the age of fifty-five years presenting with fractures of the trochanteric region caused by a low-energy injury, classified as AO/OTA Type 31-A1 and A2.\n Treatment with a sliding compression hip screw (Dynamic Hip Screw; Synthes-Stratec, Oberdorf, Switzerland) or an intramedullary nail (Proximal Femoral Nail; Synthes-Stratec, Oberdorf, Switzerland).\n Intraoperative: operative and fluoroscopy times, the difficulty of the operation, intraoperative complications, and blood loss. Radiologic: fracture healing and failure of fixation. Clinical: pain, social functioning score, and mobility score.\n The minimum follow-up was one year. We did not find any statistically significant difference, intraoperatively, radiologically, or clinically, between the two groups of patients.\n There is no advantage to an intramedullary nail versus a sliding compression hip screw for low-energy pertrochanteric fractures AO/OTA 31-A1 and A2, specifically with its increased cost and lack of evidence to show decreased complications or improved patient outcome.", "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 purpose of this study is to compare a cephalomedullary nail that uses a piriformis fossa starting point to one that uses a trochanteric starting point, in the treatment of high-energy proximal femur fractures in young patients. Our hypothesis was that a nail that uses a trochanteric starting point would result in less blood loss than a nail that uses a piriformis fossa starting point.\n Prospective, randomized.\n Level 1 trauma center.\n Thirty-four consecutive patients aged between 18 and 50 years who sustained a subtrochanteric, intertrochanteric, or ipsilateral femoral neck/shaft fracture due to a high-energy injury were enrolled.\n Patients were randomized to have their fractures repaired with a Russell-Taylor Recon Nail or Howmedica Long Gamma Nail. Surgery was performed on a fracture table, in supine or lateral position according to the surgeon's preference. Direct fracture exposure was avoided. Reduction was obtained through traction, patient positioning, and manual pressure. If necessary, stab-wound incisions were made to introduce instruments to improve reduction. Intramedullary reamers were used, and all nails were statically locked. Bone grafting was not used.\n Blood loss, incision length, duration of surgery, and body mass index were recorded for each patient. Surgeon's assessment of ease of use of the device and quality of reduction were noted. Patients were to be followed up to assess fracture union. Hip and knee ranges of motion at latest follow-up were measured. Radiographs obtained at the time of union were assessed for varus malalignment. Return to work status was recorded, and the Harris Hip Score was used to assess hip function.\n There were 17 patients in each group. The 2 groups did not differ with regard to blood loss, incision length, and duration of surgery or intraoperative complications. Body mass index was significantly linked to duration of surgery (P<0.001) and incision length (P<0.001). Surgeon's assessment of ease of use and reduction quality for the two devices did not differ. The rate of varus malunion did not differ between the 2 groups. Two patients were lost to follow-up before fracture union. All other fractures healed with no need for bone grafting or other procedures to obtain union. One obese patient developed a wound infection that resolved after debridement and a course of antibiotics. A total of 6 patients were lost prior to their 1-year follow-up visit. Among the remaining 28 patients, at an average follow-up of 14 months, no difference was noted between the 2 groups with regard to return to work status, Harris Hip Score, or hip and knee ranges of motion.\n Both devices yield predictably good results in these difficult fractures. We found no difference between the two devices with regard to incision length, duration of surgery, blood loss, reduction, ease of use, union rate, complication rate, or outcome.", "Intramedullary nailing has been the gold standard in the management of lower limb fractures by virtue of advantage of early joint mobilisation and weight bearing. They are being increasingly used in the peri-trochanteric fractures of femur. Biomechanical studies have proved the supremacy of single femoral neck screw construct over two femoral neck screws along with the intramedullary nails in osteoporotic bones due to lower incidence of complications. This randomised clinical trial was conducted to study the clinico-radiological outcome of single and two-femoral neck screw construct in the management of unstable trochanteric fractures in the elderly osteoporotic bones. Although there was no significant difference in the clinical outcome in the two groups, less sliding of the femoral neck screws was noted with two-femoral neck screw configuration. The tip-apex distance was also significantly lower in the two-screw construct compared to that of the single screw construct. This study to our knowledge is the first randomised control clinical trial evaluating the effectiveness of one and two femoral neck screw configuration of intra-medullary nails in the management of unstable trochanteric fractures.", "The current prospective and randomized study was done to determine whether fixation of intertrochanteric femoral fractures that lack a medial buttress with a dynamically locked intramedullary hip screw prevents proximal stress shielding. Stress shielding was evident by the presence of cortical hypertrophy at the level of the tip of the nail and often was associated with midthigh pain. Of the 80 patients enrolled in this trial, 64 still were alive after 1 year. Among these patients, 30 had the nail classically locked with two screws transfixing the nail in two separate holes (Group A), and 34 had the nail locked with one screw passing through a slot (Group B). The average duration of followup was 37 months (range, 12-49 months). Tolerance to dynamically locked nails was significantly better, with only one patient in Group B having cortical hypertrophy of the femur at the level of the tip of the nail, compared with six patients in Group A. Other outcomes were equal in both groups. Late tolerance to this new dynamically locked intramedullary hip screw is good, while retaining the known advantages of nailing of these fractures.", "This study aimed at comparing the results obtained with a sliding screw plate and an experimental device including a small-diameter nail that can be placed with a mini-invasive approach and provides a stable fixation.\n Randomized prospective study.\n University hospital.\n The study included two groups with thirty fractures of the trochanteric area.\n In both groups, the surgical procedure was carried out on patients placed on a traction table in a supine position, under an x-ray amplifier. Sliding screw plates (THS) were set in place according to the usual open technique. Nails were placed through a twenty-millimeter supratrochanteric cutaneous incision. This experimental system comprised a locked intramedullary nail with two nonparallel seven-millimeter cervicocephalic screws.\n The comparison between the two groups was based on the surgical procedure (time, duration of x-ray irradiation, and total blood loss); the initial postoperative period (complications, duration of hospital stay, and the time before returning home); the time before full weight bearing became effective; the functional and social recovery; mortality; and the quality of immediate and final anatomic restitution and healing.\n Operating time (p < 0.001) and blood loss (p < 0.001) were lower in the nail group, and no blood transfusion was required. Postoperative pain (p < 0.01), time necessary to support full weight bearing (p < 0.02), and time before returning home (p < 0.05) were reduced in the nail group. All fractures healed in the same amount of time, with good anatomic results in the nail group, whereas ten impactions beyond ten millimeters occurred in the plate group. No difference was found between the two groups in walking ability and autonomy recovery, but hip function (p < 0.05) was better in the nail group.\n This preliminary clinical study has shown the advantages of this mini-invasive technique. It could not evaluate all the possible disadvantages inherent in the method. These points will be evaluated in a multicenter study justified by these preliminary results." ]

[ "18047871", "16753335", "17872930", "18223016", "11601430", "11588611", "16564618", "14746870", "19594842" ]

[ "The effect of a series of repetitive transcranial magnetic stimulations of the motor cortex on central pain after spinal cord injury.", "Transcranial magnetic stimulation for pain control. Double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy.", "Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia.", "Motor cortex rTMS in chronic neuropathic pain: pain relief is associated with thermal sensory perception improvement.", "Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex.", "Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex.", "A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury.", "Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I.", "A pilot study investigating the effects of fast left prefrontal rTMS on chronic neuropathic pain." ]

[ "To study the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on central pain in patients with chronic spinal cord injury (SCI).\n Double-blind randomized controlled trial. Mean follow-up period was 4.5 weeks.\n General hospital.\n Twelve paraplegic patients due to thoracic SCI suffering chronic central pain (11 completed the study) who were randomly selected from a list of eligible patients.\n Real or sham 10 daily motor rTMS treatments (500 trains at 5 Hz for 10 s; total of 500 pulses at intensity of 115% of motor threshold) using figure-of-8 coil over the vertex.\n Chronic pain intensity (visual analog scale [VAS], McGill Pain Questionnaire [MPQ]), pain threshold, and level of depression (Beck Depression Inventory).\n Both real and sham TMS induced a similar, significant reduction in VAS scores (P<.001) immediately after each of the 10 treatment sessions and in VAS and MPQ scores after the end of the treatment series. However, only real rTMS conferred a significant increase in heat-pain threshold (4 degrees C, P<.05) by the end of the series. Most important, the reduction in MPQ scores in the real rTMS group continued during the follow-up period. Depression scores were equally reduced in both groups but similar to pain relief, depression continued to improve at follow-up in the real rTMS group.\n Whereas the pain alleviation induced by a single rTMS treatment is probably due to placebo, patients with SCI may benefit from a series of rTMS treatments.", "To assess, using a double-blind procedure, the pain-relieving effects of rTMS against placebo, and their predictive value regarding the efficacy of implanted motor cortex stimulation (MCS).\n Three randomised, double-blinded, 25 min sessions of focal rTMS (1 Hz, 20 Hz and sham) were performed in 12 patients, at 2 weeks intervals. Effects on pain were estimated from daily scores across 5 days before, and 6 days after each session. Analgesic effects were correlated with those of subsequent implanted motor cortex stimulation (MCS).\n Immediately after the stimulating session, pain scores were similarly decreased by all rTMS modalities. Conversely, during the following week, 1 Hz stimulation provided significantly less analgesia than 20 Hz and placebo, and was pro-algesic in some patients. Placebo and 20 Hz rTMS were effective on different patients, and only 20 Hz rTMS predicted the efficacy of subsequent MCS, with no false positives.\n While 1Hz rTMS should not be used with analgesic purposes, high-frequency rTMS may become useful to select candidates for MCS. Placebo effects are powerful and should be controlled for. Immediate results after a single rTMS session are misleading.\n Defining rTMS parameters is a crucial step before proposing rTMS as predictive test of SCM efficacy in clinical practice.", "Non-invasive unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex induces analgesic effects in focal chronic pain syndromes, probably by modifying central pain modulatory systems. Neuroimaging studies have shown bilateral activation of a large number of structures, including some of those involved in pain processing, suggesting that such stimulation may induce generalized analgesic effects. The goal of this study was to assess the effects of unilateral rTMS of the motor cortex on chronic widespread pain in patients with fibromyalgia. Thirty patients with fibromyalgia syndrome (age: 52.6 +/- 7.9) were randomly assigned, in a double-blind fashion, to two groups, one receiving active rTMS (n = 15) and the other sham stimulation (n = 15), applied to the left primary motor cortex in 10 daily sessions. The primary outcome measure was self-reported average pain intensity over the last 24 h, measured at baseline, daily during the stimulation period and then 15, 30 and 60 days after the first stimulation. Other outcome measures included: sensory and affective pain scores for the McGill pain Questionnaire, quality of life (assessed with the pain interference items of the Brief Pain Inventory and the Fibromyalgia Impact Questionnaire), mood and anxiety (assessed with the Hamilton Depression Rating Scale, the Beck Depression Inventory and the Hospital Anxiety and Depression Scale). We also assessed the effects of rTMS on the pressure pain threshold at tender points ipsi- and contralateral to stimulation. Follow-up data were obtained for all the patients on days 15 and 30 and for 26 patients (13 in each treatment group) on day 60. Active rTMS significantly reduced pain and improved several aspects of quality of life (including fatigue, morning tiredness, general activity, walking and sleep) for up to 2 weeks after treatment had ended. The analgesic effects were observed from the fifth stimulation onwards and were not related to changes in mood or anxiety. The effects of rTMS were more long-lasting for affective than for sensory pain, suggesting differential effects on brain structures involved in pain perception. Only few minor and transient side effects were reported during the stimulation period. Our data indicate that unilateral rTMS of the motor cortex induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia.", "Improvement in sensory detection thresholds was found to be associated with neuropathic pain relief produced by epidural motor cortex stimulation with surgically implanted electrodes.\n To determine the ability of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex to produce similar sensory changes.\n In 46 patients with chronic neuropathic pain of various origins, first-perception thresholds for thermal (cold, warm) and mechanical (vibration, pressure) sensations were quantified in the painful zone and in the painless homologue contralateral territory, before and after rTMS of the motor cortex corresponding to the painful side. Ongoing pain level was also scored before and after rTMS. Three types of rTMS session, performed at 1 Hz or 10 Hz using an active coil, or at 10 Hz using a sham coil, were compared. The relationships between rTMS-induced changes in sensory thresholds and in pain scores were studied.\n Subthreshold rTMS applied at 10 Hz significantly lowered pain scores and thermal sensory thresholds in the painful zone but did not lower mechanical sensory thresholds. Pain relief correlated with post-rTMS improvement of warm sensory thresholds in the painful zone.\n Thermal sensory relays are potentially dysfunctioning in chronic neuropathic pain secondary to sensitisation or deafferentation-induced disinhibition. By acting on these structures, motor cortex stimulation could relieve pain and concomitantly improve innocuous thermal sensory discrimination.", "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.", "Chronic electrical stimulation of the precentral (motor) cortex using surgically implanted electrodes is performed to treat medication-resistant neurogenic pain. The goal of this placebo-controlled study was to obtain such antalgic effects by means of a non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS). Eighteen patients with intractable neurogenic pain of various origins were included and underwent a 20 min session of either 10 Hz, 0.5 Hz or* sham rTMS over the motor cortex in a random order. A significant decrease in the mean pain level of the series was obtained only after 10 Hz rTMS. This study shows that a transient pain relief can be induced by 10 Hz rTMS of the motor cortex in some patients suffering from chronic neurogenic pain.", "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.", "In complex regional pain syndrome (CRPS) many clinical symptoms suggest involvement of the central nervous system. Neuropathic pain as the leading symptom is often resistant to therapy. In the present study we investigated the analgesic efficiency of repetitive transcranial magnetic simulation (rTMS) applied to the motor cortex contralateral to the CRPS-affected side. Seven out of ten patients reported decreased pain intensities. Pain relief occurred 30 s after stimulation, whereas the maximum effect was found 15 min later. Pain re-intensified increasingly 45 min after rTMS. In contrast, sham rTMS did not alter pain perception. These findings provide evidence that in CRPS I pain perception can be modulated by repetitive motor cortex stimulation.", "Stimulating the human cortex using transcranial magnetic stimulation (TMS) temporarily reduces clinical and experimental pain; however, it is unclear which cortical targets are the most effective. The motor cortex has been a popular target for managing neuropathic pain, while the prefrontal cortex has been investigated for an array of nociceptive pain conditions. It is unclear whether the motor cortex is the only effective cortical target for managing neuropathic pain, and no published studies to date have investigated the effects of prefrontal stimulation on neuropathic pain.\n This preliminary pilot trial employed a sham-controlled, within-subject, crossover design to evaluate clinical pain as well as laboratory pain thresholds among four patients with chronic neuropathic pain. Each participant underwent three real and three sham 20-minute sessions of 10 Hz left prefrontal repetitive TMS. Daily pain diaries were collected for 3 weeks before and after each treatment phase along with a battery of self-report pain and mood questionnaires.\n Time-series analysis at the individual patient level indicated that real TMS was associated with significant improvements in average daily pain in 3 of the 4 participants. These effects were independent of changes in mood in two of the participants. At the group level, a decrease of 19% in daily pain on average, pain at its worst, and pain at its least was observed while controlling for changes in mood, activity level and sleep. The effects of real TMS were significantly greater than sham. Real TMS was associated with increases in thermal and mechanical pain thresholds, whereas sham was not. No statistically significant effects were observed across the questionnaire data.\n The prefrontal cortex may be an important TMS cortical target for managing certain types of pain, including certain neuropathic pain syndromes." ]

[ "20200346", "15883262", "12205648", "15326073", "11176731", "15325833", "16034009", "19933787", "16899775" ]

[ "Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe.", "Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results.", "Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26-week randomized, placebo-controlled, double-blind trial.", "Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study.", "Use of the statins in patients after acute myocardial infarction: does evidence change practice?", "Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.", "Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis.", "The Enhancing Secondary Prevention in Coronary Artery Disease trial.", "High-dose atorvastatin after stroke or transient ischemic attack." ]

[ "There is some evidence that statins may have a protective and symptomatic benefit in Alzheimer disease (AD). The LEADe study is a randomized controlled trial (RCT) evaluating the efficacy and safety of atorvastatin in patients with mild to moderate AD.\n This was an international, multicenter, double-blind, randomized, parallel-group study. Subjects had mild to moderate probable AD (Mini-Mental State Examination score 13-25), were aged 50-90 years, and were taking donepezil 10 mg daily for > or 3 months prior to screening. Entry low-density lipoprotein cholesterol levels (LDL-C) were > 95 and < 195 mg/dL. Patients were randomized to atorvastatin 80 mg/day or placebo for 72 weeks followed by a double-blind, 8-week atorvastatin withdrawal phase. Coprimary endpoints were changes in cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog]) and global function (Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS-CGIC]) at 72 weeks.\n A total of 640 patients were randomized in the study. There were no significant differences in the coprimary endpoints of ADAS-cog or ADCS-CGIC or the secondary endpoints. Atorvastatin was generally well-tolerated.\n In this large-scale randomized controlled trial evaluating statin therapy as a treatment for mild to moderate Alzheimer disease, atorvastatin was not associated with significant clinical benefit over 72 weeks. This treatment was generally well-tolerated without unexpected adverse events. Classification of evidence: This study provides Class II evidence that intensive lipid lowering with atorvastatin 80 mg/day in patients with mild to moderate probable Alzheimer disease (aged 50-90), taking donepezil, with low-density lipoprotein cholesterol levels between 95 and 195 mg/dL over 72 weeks does not benefit cognition (as measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale) (p = 0.26) or global function (as measured by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change) (p = 0.73) compared with placebo.", "Laboratory evidence of cholesterol-induced production of amyloid beta as a putative neurotoxin precipitating Alzheimer disease, along with epidemiological evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder.\n To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in patients with mild to moderate Alzheimer disease.\n Pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covariance as the primary method of statistical assessment.\n Individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination score of 12-28) were recruited. Of the 98 participants providing informed consent, 71 were eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable.\n The primary outcome measures were change in Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale scores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. The tertiary outcome measures included total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels.\n Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This beneficial effect reached significance for the Geriatric Depression Scale and the Alzheimer's Disease Assessment Scale-cognitive subscale at 6 months and was significant at the level of a trend for the Alzheimer's Disease Assessment Scale-cognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward.\n Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.", "In a randomized, placebo-controlled, double-blind study, we investigated whether statins alter cholesterol metabolites and reduce Abeta levels in the cerebrospinal fluid of 44 patients with Alzheimer's disease. Individuals were given up to 80mg simvastatin daily or placebo for 26 weeks. Overall, simvastatin did not significantly alter cerebrospinal fluid levels of Abeta40 and Abeta42. In post hoc analysis, simvastatin significantly decreased Abeta40 levels in the cerebrospinal fluid of patients with mild Alzheimer's disease. The reduction of Abeta40 correlated with the reduction of 24S-hydroxycholesterol. These changes were not observed in more severely affected patients.", "Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome (ACS). We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol (LCL-C) lowering. The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS.\n Seventy patients with ACS were enrolled. All patients underwent emergency coronary angiography and percutaneous coronary intervention (PCI). They were randomized to intensive lipid-lowering therapy (n=35; atorvastatin 20 mg/d) or control (n=35) groups after PCI. Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients (atorvastatin, n=24; control, n=24). LDL-C level was significantly decreased by 41.7% in the atorvastatin group compared with the control group, in which LDL-C was increased by 0.7% (P<0.0001). Plaque volume was significantly reduced in the atorvastatin group (13.1+/-12.8% decrease) compared with the control group (8.7+/-14.9% increase; P<0.0001). Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level (R=0.456, P=0.0011) and percent LDL-C reduction (R=0.612, P<0.0001), even in patients with baseline LDL-C <125 mg/dL.\n Early aggressive lipid-lowering therapy by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS. Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction, even in patients with low baseline LDL-C.", "To compare the use of lipid-lowering agents in 42 628 elderly patients (aged > or =65 years) after acute myocardial infarction, before and after the publication of the Scandinavian Simvastatin Survival Study (4S), using the Ontario Myocardial Infarction Database.\n Multivariate regression models were created to estimate changes in the rate of statin use over time in monthly cohorts of elderly patients after acute myocardial infarction in Ontario from April 1, 1992, to March 31, 1997. Changes in the rate of statin use over time were estimated using patient and prescriber characteristics.\n We found a 3.6-fold significant increase in the monthly rate of statin use after the publication of 4S compared with before the publication of 4S (P<.001); specifically, the rate of increase in simvastatin and pravastatin sodium use was higher after the publication of 4S (P<.001 for each). Before the publication of 4S, the rate of increase in statin use in younger patients (aged 65-74 years) was 2.7 times higher than in older patients (aged > or =75 years) (P =.02), while after the publication of 4S, the rate of increase in statin use was only 1.8-fold higher in the younger group (P<.001). After the publication of 4S, there was a 1.6-fold higher rate of increase in statin use in male compared with female patients (P =.006). Also after the publication of 4S, specialists (cardiologists and internists) had a 2-fold higher rate of increased use of the statins than did generalists (P<.001).\n It is possible to shift practice if the evidence of benefit is strong, the intervention is easy to implement, and the intervention is marketed aggressively.", "Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease, but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined. We aimed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol.\n 2838 patients aged 40-75 years in 132 centres in the UK and Ireland were randomised to placebo (n=1410) or atorvastatin 10 mg daily (n=1428). Study entrants had no documented previous history of cardiovascular disease, an LDL-cholesterol concentration of 4.14 mmol/L or lower, a fasting triglyceride amount of 6.78 mmol/L or less, and at least one of the following: retinopathy, albuminuria, current smoking, or hypertension. The primary endpoint was time to first occurrence of the following: acute coronary heart disease events, coronary revascularisation, or stroke. Analysis was by intention to treat.\n The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met. Median duration of follow-up was 3.9 years (IQR 3.0-4.7). 127 patients allocated placebo (2.46 per 100 person-years at risk) and 83 allocated atorvastatin (1.54 per 100 person-years at risk) had at least one major cardiovascular event (rate reduction 37% [95% CI -52 to -17], p=0.001). Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years. Assessed separately, acute coronary heart disease events were reduced by 36% (-55 to -9), coronary revascularisations by 31% (-59 to 16), and rate of stroke by 48% (-69 to -11). Atorvastatin reduced the death rate by 27% (-48 to 1, p=0.059). No excess of adverse events was noted in the atorvastatin group.\n Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events, including stroke, in patients with type 2 diabetes without high LDL-cholesterol. No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins. The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld.", "Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus. However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined.\n We conducted a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo. The primary end point was a composite of death from cardiac causes, nonfatal myocardial infarction, and stroke. Secondary end points included death from all causes and all cardiac and cerebrovascular events combined.\n After four weeks of treatment, the median level of low-density lipoprotein cholesterol was reduced by 42 percent among patients receiving atorvastatin, and among those receiving placebo it was reduced by 1.3 percent. During a median follow-up period of four years, 469 patients (37 percent) reached the primary end point, of whom 226 were assigned to atorvastatin and 243 to placebo (relative risk, 0.92; 95 percent confidence interval, 0.77 to 1.10; P=0.37). Atorvastatin had no significant effect on the individual components of the primary end point, except that the relative risk of fatal stroke among those receiving the drug was 2.03 (95 percent confidence interval, 1.05 to 3.93; P=0.04). Atorvastatin reduced the rate of all cardiac events combined (relative risk, 0.82; 95 percent confidence interval, 0.68 to 0.99; P=0.03, nominally significant) but not all cerebrovascular events combined (relative risk, 1.12; 95 percent confidence interval, 0.81 to 1.55; P=0.49) or total mortality (relative risk, 0.93; 95 percent confidence interval, 0.79 to 1.08; P=0.33).\n Atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis.", "Proven efficacious therapies are sometimes underused in patients with chronic cardiac conditions, resulting in suboptimal outcomes. We evaluated whether evidence summaries, which were either unsigned or signed by local opinion leaders, improved the quality of secondary prevention care delivered by primary care physicians of patients with coronary artery disease.\n We performed a randomized trial, clustered at the level of the primary care physician, with 3 study arms: control, unsigned statements or opinion leader statements. The statements were faxed to primary care physicians of adults with coronary artery disease at the time of elective cardiac catheterization. The primary outcome was improvement in statin management (initiation or dose increase) 6 months after catheterization.\n We enrolled 480 adults from 252 practices. Although statin use was high at baseline (n=316 [66%]), most patients were taking a low dose (mean 32% of the guideline-recommended dose), and their low-density lipoprotein (LDL) cholesterol levels were elevated (mean 3.09 mmol/L). Six months after catheterization, statin management had improved in 79 of 157 patients (50%) in the control arm, 85 of 158 (54%) patients in the unsigned statement group (adjusted odds ratio [OR] 1.18, 95% CI 0.71-1.94, p=0.52) and 99 of 165 (60%) patients in the opinion leader statement group (adjusted OR 1.51, 95% CI 0.94-2.42, p=0.09). The mean fasting LDL cholesterol levels after 6 months were similar in all 3 study arms: 2.35 (standard deviation [SD] 0.86) mmol/L in the control arm compared with 2.24 (SD 0.73) among those in the opinion leader group (p=0.48) and 2.19 (SD 0.68) in the unsigned statement group (p=0.32).\n Faxed evidence reminders for primary care physicians, even when endorsed by local opinion leaders, were insufficient to optimize the quality of care for adults with coronary artery disease. ClinicalTrials.gov trial register no. NCT00175240.", "Statins reduce the incidence of strokes among patients at increased risk for cardiovascular disease; whether they reduce the risk of stroke after a recent stroke or transient ischemic attack (TIA) remains to be established.\n We randomly assigned 4731 patients who had had a stroke or TIA within one to six months before study entry, had low-density lipoprotein (LDL) cholesterol levels of 100 to 190 mg per deciliter (2.6 to 4.9 mmol per liter), and had no known coronary heart disease to double-blind treatment with 80 mg of atorvastatin per day or placebo. The primary end point was a first nonfatal or fatal stroke.\n The mean LDL cholesterol level during the trial was 73 mg per deciliter (1.9 mmol per liter) among patients receiving atorvastatin and 129 mg per deciliter (3.3 mmol per liter) among patients receiving placebo. During a median follow-up of 4.9 years, 265 patients (11.2 percent) receiving atorvastatin and 311 patients (13.1 percent) receiving placebo had a fatal or nonfatal stroke (5-year absolute reduction in risk, 2.2 percent; adjusted hazard ratio, 0.84; 95 percent confidence interval, 0.71 to 0.99; P=0.03; unadjusted P=0.05). The atorvastatin group had 218 ischemic strokes and 55 hemorrhagic strokes, whereas the placebo group had 274 ischemic strokes and 33 hemorrhagic strokes. The five-year absolute reduction in the risk of major cardiovascular events was 3.5 percent (hazard ratio, 0.80; 95 percent confidence interval, 0.69 to 0.92; P=0.002). The overall mortality rate was similar, with 216 deaths in the atorvastatin group and 211 deaths in the placebo group (P=0.98), as were the rates of serious adverse events. Elevated liver enzyme values were more common in patients taking atorvastatin.\n In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke. (ClinicalTrials.gov number, NCT00147602 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society." ]

[ "12600912", "20104528", "12124559", "11072938", "18285698", "9684133", "12900820", "15599680", "9197872" ]

[ "The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: a randomized, controlled trial.", "Incidence of cancers, ischemic cardiovascular diseases and mortality during 5-year follow-up after stopping antioxidant vitamins and minerals supplements: a postintervention follow-up in the SU.VI.MAX Study.", "Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation?", "Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial.", "Effects of low- and high-flux dialyzers on oxidative stress and insulin resistance.", "Antioxidant treatment during liver resection for alleviation of ischemia-reperfusion injury.", "Effects of exercise training on coronary heart disease risk factors in renal transplant recipients.", "[Investigation of antioxidant therapy with sodium selenite in acute pancreatitis. A prospective randomized blind trial].", "Antioxidants in the treatment of severe pre-eclampsia: an explanatory randomised controlled trial." ]

[ "Patients with end-stage renal failure have increased oxidative stress and show elevated cardiovascular mortality. Whether increased cardiovascular events can be prevented by the administration of antioxidants is unknown.\n We evaluated the effects of acetylcysteine, a thiol-containing antioxidant, on cardiovascular events in patients undergoing hemodialysis. A prospective, randomized, placebo-controlled trial was conducted between October 1, 1999, and September 30, 2001, in 134 patients (76 male and 58 female) with a mean age of 62+/-16 years (mean+/-SD) who had been undergoing maintenance hemodialysis for a minimum of 3 months 3 times weekly in an ambulatory center. Median (range) follow-up was 14.5 (1 to 24) months. Patients were randomly assigned either to receive acetylcysteine (600 mg BID) or placebo. The primary end point was a composite variable consisting of cardiac events including fatal and nonfatal myocardial infarction, cardiovascular disease death, need for coronary angioplasty or coronary bypass surgery, ischemic stroke, peripheral vascular disease with amputation, or need for angioplasty. Secondary end points included each of the component outcomes, total mortality, and cardiovascular mortality. A total of 18 (28%) of the 64 hemodialysis patients assigned to acetylcysteine group and 33 (47%) of the 70 hemodialysis patients assigned to control group had a primary end point (relative risk, 0.60 [95% CI, 0.38 to 0.95], P=0.03). No significant differences in secondary end points or total mortality were detected.\n In hemodialysis patients, treatment with acetylcysteine (600 mg BID) reduces composite cardiovascular end points.", "The Supplementation in Vitamins and Mineral Antioxidants Study was a double-blind, placebo-controlled, randomized trial, in which 12,741 French adults (7,713 women aged 35-60 years and 5,028 men aged 45-60 years) received a combination of ascorbic acid (120 mg), vitamin E (30 mg), beta-carotene (6 mg), selenium (100 microg) and zinc (20 mg), or placebo daily for a median follow-up time of 7.5 years [October 1994 to September 2002]. Antioxidant supplementation decreased total cancer incidence and total mortality in men. Postintervention follow-up assessment of total cancer incidence, ischemic cardiovascular disease incidence and total mortality was carried out for 5 years [September 1, 2002, to September 1, 2007]. No late effect of antioxidant supplementation was revealed 5 years after ending the intervention neither on ischemic cardiovascular disease incidence and mortality in both genders nor on cancer incidence in women. Regarding duration of intervention effects in men, the reduced risk of total cancer incidence and total mortality was no longer evident after the 5-year postintervention follow-up. During the postsupplementation period, the relative risk (RR) for total cancer incidence (n = 126) was 0.98 (95% confidence interval [CI], 0.75-1.27) among antioxidant recipients compared to nonrecipients. For total mortality (n = 90), the RR was 0.98 (95% CI, 0.75-1.26) for men receiving antioxidants compared to nonrecipients. In conclusion, beneficial effects of antioxidant supplementation in men disappeared during postintervention follow-up.", "Renal failure after lower torso ischemia is a serious problem, partly caused by hypotension and indirect reperfusion injury. This injury is partly due to the formation of oxygen free radicals by activated neutrophils. This injury results in albuminuria and renal function impairment. There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion.\n In this prospective randomised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair. The patients received either standard treatment (n=22) or standard treatment with additional antioxidants perioperatively (Allopurinol, vitamin E and C, N-acetylcysteine and mannitol). For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance.\n Despite significantly increased serum total antioxidant capacity, the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine. There was however a significantly higher creatinine clearance in this group at day 2.\n The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy.", "Excess cardiovascular mortality has been documented in chronic haemodialysis patients. Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without, suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis. We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease.\n Haemodialysis patients with pre-existing cardiovascular disease (n=196) aged 40-75 years at baseline from six dialysis centres were enrolled and randomised to receive 800 IU/day vitamin E or matching placebo. Patients were followed for a median 519 days. The primary endpoint was a composite variable consisting of: myocardial infarction (fatal and non-fatal), ischaemic stroke, peripheral vascular disease (excluding the arteriovenous fistula), and unstable angina. Secondary outcomes included each of the component outcomes, total mortality, and cardiovascular-disease mortality.\n A total of 15 (16%) of the 97 patients assigned to vitamin E and 33 (33%) of the 99 patients assigned to placebo had a primary endpoint (relative risk 0.46 [95% CI 0.27-0.78], p=0.014). Five (5.1%) patients assigned to vitamin E and 17 (17.2%) patients assigned to placebo had myocardial infarction (0.3 [0.11-0.78], p=0.016). No significant differences in other secondary endpoints, cardiovascular disease, or total mortality were detected.\n In haemodialysis patients with prevalent cardiovascular disease, supplementation with 800 IU/day vitamin E reduces composite cardiovascular disease endpoints and myocardial infarction.", "Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease (ESRD). The cornerstone of high CVD incidence in ESRD patients is endothelial dysfunction which results from inflammation, oxidative stress and insulin resistance. Although various modalities of hemodialysis (HD) have been presumed to exert different effects on oxidative stress and insulin resistance, solid evidence is still lacking.\n 40 ESRD patients undergoing HD were prospectively enrolled and divided randomly into two groups. Patients in each group received either F8 HPS (low-flux) (Group A) or FX80 (high-flux) (Group B) as HD dialyzers for 2 consecutive months. Diet pattern and medications were kept as usual in both groups to avoid considerable blood glucose change during study period. Blood samples were taken at the start and end of the study.\n A total of 38 patients (18 and 20 for Groups A and B, respectively) completed the study. Within each group, there was no change in adiponectin, plasma 8-iso-prostaglandin F(2)(alpha), high-sensitivity C-reactive protein, blood glucose and insulin after 2 months of treatment except a significant change of HOMA(IR) (p = 0.02) in high-flux group. The significant change of HOMA(IR) between the two groups (p = 0.017) mainly results from the parallel change of insulin between the two groups (p = 0.03).\n For patients receiving HD, the high-flux dialyzer with synthetic polysulfone membranes fails to provide a better anti-inflammatory or antioxidative effect than the low-flux dialyzer; however, the high-flux dialyzer does significantly improve insulin resistance in this short-term study. This result implies that the high-flux dialyzer might provide better cardiovascular protection than the low-flux dialyzer. Therefore, the low-flux dialyzer might be considered for patients who only need short-term HD therapy. Regarding patients under long-term maintenance HD therapy, a high-flux dialyzer might be the choice of dialyzer.\n Copyright 2008 S. Karger AG, Basel.", "Many experimental studies on ischemia-reperfusion injury in animals suggest a preventive effect of antioxidants, but the clinical significance of these findings is still unclear. The aim of our study was to evaluate the effect of antioxidant treatment with vitamins on liver function parameters during liver resection.\n Our prospective randomized study comprised 58 patients undergoing major liver surgery, including the Pringle maneuver. In the treatment group 32 patients received a multivitamin infusion (Omnibionta) which included 10 mg of alpha-tocopherol acetate, 2 mg of DL-alpha-tocopherol and 1 g of ascorbate. The control group consisted of 26 patients. Various parameters associated with liver function, such as transaminases, lactate, ammonia, bilirubin, cholinesterase and clotting parameters were measured preoperatively, at the beginning of liver ischemia, 15, 30 and 60 minutes after reperfusion onset and every 12 hours after the operation.\n The Mann-Whitney-Wilcoxon-Test showed statistically significant differences in the postischemic changes between the treatment group and the control group for the Quick test (prothrombin time): p = 0.01. The transaminases were also markedly better in the treatment group (splitting-up slightly more delayed than with the Quick test). A smaller effect was seen with cholinesterase. Lactate, however, increased intraoperatively with a strong correlation to the duration of ischemia and returned quickly to baseline values without any remarkable influence of the antioxidant treatment.\n In our study, antioxidant treatment with a multivitamin infusion showed a positive effect on postischemic liver function parameters.", "Multiple risk-factor interventions that include lifestyle changes have been proved to be effective in reducing risk profile in persons at high risk for developing coronary heart disease (CHD). There have not been similar studies involving transplant recipients. The purpose of this study is to examine effects of exercise training on cardiovascular risk profile during the first year after renal transplantation. We used traditional CHD risk factors and the Framingham CHD prediction methods.\n Ninety-six transplant recipients were randomly assigned to 2 groups at 1 month posttransplantation: the exercise training (EX group; n = 51) and usual care groups (UC group; n = 45). Testing was performed at baseline and 12 months posttransplantation and included maximal exercise testing and evaluation of CHD risk factors and risk-factor categories, determined by means of the Framingham equations.\n Overall 10-year CHD risk score did not change in either group. All patients showed increases in total cholesterol (TC) level, high-density lipoprotein fraction of cholesterol (HDL-C), and body mass index over time. No differences were observed between groups, except for a trend toward greater improvement in HDL cholesterol levels in the EX group (P = 0.07). Significantly more patients in the EX group moved out of the high-risk category in TC-HDL ratio. All patients remained in the high-risk category for physical fitness. There was a significant negative correlation of CHD risk and maximal exercise capacity (r = -0.406; P < 0.001).\n Exercise training alone does not reduce CHD risk during the first year after transplantation. Research to determine the effects of multiple risk interventions during a longer period in transplant recipients is warranted.", "Oxygen free radicals appear in the early phase of acute pancreatitis followed by an imbalance between the oxygen and anti-oxygen system. Sodium selenite may play an important role in the reduction of radicals in experimental pancreatitis. The aim of this study was to evaluate the effects of selenium in a clinical prospective trial.\n 70 patients with acute pancreatitis were prospectively allocated to a selenium and a placebo group. Clinical and paraclinical parameters were investigated with a follow-up of 90 days after hospital stay.\n The clinical course of the two treatment groups did not show statistically significant differences. Five patients in the selenium and three patients in the placebo group died. Depending on selenium therapy, antioxidant substances were presented in higher levels. All 17 clinical parameters showed no statistical significance.\n Substitution of sodium selenite has no beneficial effect on the clinical outcome of patients with acute pancreatitis.", "To determine whether antioxidant therapy alters the disease process in severe early onset pre-eclampsia, in support of the hypothesis that increased lipid peroxides and reactive oxygen species production-play an important role in the pathogenesis of the disease.\n Randomised, double-blind, placebo controlled trial.\n Two tertiary care, referral hospitals in Johannesburg, South Africa.\n Women with severe pre-eclampsia diagnosed between 24 and 32 weeks of gestation.\n Combined antioxidant treatment with vitamin E (800 IU/day), vitamin C (1000 mg/day), and allopurinol (200 mg/day).\n Primary outcomes: 1. prolongation of pregnancy and 2, biochemical assessment of lipid peroxides and antioxidants. Secondary outcomes: data on maternal complications, side effects of treatment, infant outcomes and regular assessment of haematologic and renal parameters.\n The proportion of women delivered within 14 days in the antioxidant group was 52% (14/27) compared with 76% (22/29) in the placebo group (relative risk 0.68, 95% confidence interval 0.45-1.04). One woman in each group had eclampsia. Eleven women (42%) in the antioxidant and 16 (59%) in the placebo group required two antihypertensives for blood pressure control. Trial medications were well tolerated with few side effects. Lipid peroxide levels were not significantly altered in the antioxidant and placebo groups. Serum uric acid levels decreased and vitamin E levels increased significantly.\n The results of this explanatory randomised trial do not encourage the routine use of antioxidants against pre-eclampsia. However, further research with modified strategies such as earlier initiation of therapy or different combinations seem worthwhile." ]

[ "9407981", "12548410", "8969668", "3554492", "1991422", "10678027", "12380728", "15543373", "9517746" ]

[ "Randomized controlled trial of primary fistulotomy with drainage alone for perianal abscesses.", "Randomized clinical trial comparing simple drainage of anorectal abscess with and without fistula track treatment.", "Prospective randomized trial of drainage alone vs. drainage and fistulotomy for acute perianal abscesses with proven internal opening.", "A randomized trial of fistulotomy in perianal abscess.", "Treatment of anorectal abscess with or without primary fistulectomy. Results of a prospective randomized trial.", "[Primary curative incision in the treatment of perianorectal abscess].", "Routine use of setons for the treatment of anal fistulae.", "Radiofrequency fistulotomy: a better alternative for treating low anal fistula.", "Prophylactic abdominal drainage after elective colonic resection and suprapromontory anastomosis: a multicenter study controlled by randomization. French Associations for Surgical Research." ]

[ "Primary fistulotomy may be advantageous for perianal abscesses because unlike ischiorectal abscesses, fistulas are more commonly found and can be laid open with full preservation of the external anal sphincters. Therefore, a randomized, controlled trial was conducted to compare primary fistulotomy with incision and drainage alone, specifically for perianal abscesses.\n Fifty-two consecutive patients (43 males; mean age, 40 (standard error of mean, 2) years) with perianal abscesses were randomized to treatment by either incision and drainage (controls; N = 28) or fistulotomy (N = 24). Patients were followed up clinically for a mean of 15.5 (standard error of the mean, 0.7) months. Anorectal manometry was also performed before, six weeks, and three months after surgery.\n Persistent fistulas developing after surgery were significantly more common after incision and drainage (N = 7; 25 percent) than after fistulotomy (N = 0; P = 0.009). One patient in each group was also found to have a residual abscess, which required repeat drainage. All patients remained fully continent. The anal pressures after incision and drainage and fistulotomy were not significantly different. Operative time, hospital stay, and time for the wound to heal completely were the same in both groups.\n Primary fistulotomy at the time of drainage for perianal abscesses results in fewer persistent fistulas and no added risk of fecal incontinence.", "Anal abscess is a frequent acute proctological disorder and whether the underlying fistula should be treated at the same time when the abscess is drained remains controversial. We examined indications for drainage alone versus drainage plus fistulotomy in terms of recurrence and continence.\n We carried out a randomized prospective study of 200 consecutive patients with anal abscess. One group received drainage alone, while in the other group drainage plus fistulotomy was performed when a subcutaneous-mucosa, low transsphincteral, or intersphincteral fistula was found. Delayed progressive fistulotomy with suture threads was performed in cases of high transsphincteric or suprasphincteric fistula.\n The internal opening of the fistula track was found in 83% of the patients. The recurrence rate was related to the surgical technique employed: 29% in the group with drainage alone and 5% in the group for which treatment of the fistula track was attempted. The incontinence rate was also related to the surgical option. In those receiving drainage and treatment of the fistula track incontinence was restricted mostly to patients with delayed fistulotomy (36.7%), compared to 2.8% of patients when simple fistulotomy was performed. There was no incontinence in the drainage alone group.\n Drainage of anal abscess with fistulotomy can be safely performed in cases of subcutaneous, intersphincteral, or low transsphincteral fistulae with a minimal recurrence rate. However, drainage alone and posterior treatment of the fistula track is recommended for high transsphincteral or suprasphincteral fistulae.", "Incision and drainage (I & D) with concurrent or delayed fistulotomy is the usual treatment for abscess-fistula with a demonstrated internal opening. We compared incision and drainage alone vs. with concurrent fistulotomy for perianal abscesses with a demonstrated internal opening.\n Consecutive patients with acute perianal abscesses and a demonstrated internal opening were prospectively randomized into either the I & D group or drainage with concurrent fistulotomy group. They were followed up at one month, three months, and one year.\n The I & D group had 21 patients, and the fistulotomy group had 24 patients. Thirteen patients had low intersphincteric abscess-fistula, and seven had low transsphincteric fistulas in the I & D group. The fistulotomy group had 9 intersphincteric abscess-fistula compared with 14 low transsphincteric ones. Median duration of surgery, hospital stay, and continence at final follow-up were the same in the two groups. Three had recurrent abscess-fistula in the I & D group compared with none in the fistulotomy group (P = 0.09).\n I & D alone for acute anal abscess-fistula with demonstrated internal opening showed a tendency to recurrence that did not reach a statistically significant difference compared with concurrent fistulotomy. I & D, therefore, puts only a few patients at risk for recurrence.", "In a randomized trial we compared the treatment of perianal abscess by incision only (18 patients) with that by incision followed by fistulotomy 3 days later (20 patients). All patients were observed for 12 months. There were no differences between the two groups with regard to recurrent abscess/fistula, but the fistulotomy group had a statistically significantly higher prevalence of flatus incontinence. Further, fistulotomy was followed by significantly longer duration of hospitalization and by delayed healing. We recommend that fistulotomy is used only in patients with recurrent abscess.", "To determine whether primary fistulectomy should be performed or not at the time of incision and drainage, a prospective, randomized study in 70 patients with anorectal abscess was conducted. Thirty-six patients underwent incision, drainage and fistulectomy with primary partial internal spincterectomy (group I), whereas in 34 patients anorectal abscess was treated by incision and drainage alone (group II). After a median follow-up of 42.5 months, the combined recurrence or persistence rate was 2.9 percent in group I and 40.6 percent in group II (P less than 0.0003, log-rank test). Recurrent abscesses or persistent fistulas were treated by secondary partial internal sphincterectomy. Comparing anal continence before and 1 year after definite treatment, we found increased anal function disturbances in 39.4 percent of the patients in group I and in 21.4 percent of the patients in group II (P less than 0.106, Fisher-exact test). The combined recurrence or persistence rate of 40.6 percent indicates that more than half of the patients with anorectal abscess will have no further problems after simple incision and drainage. This finding, as well as the increased anal function disturbances after partial internal sphincterectomy (either primary or secondary) are the main reasons to reserve fistulectomy as a second stage procedure if necessary.", "More than 50% of the patients with perianorectal abscess treated with traditional incisional drainage will lead to fistula formation postoperatively. We present a procedure of primary curative incision for treatment with perianorectal abscess without fistula formation. The result of primary curative incision in comparison with traditional incisional drainage in a randomized control study showed that the incidence of postoperative fistula formation and recurrent abscess was 2.56% in the former and 56.25% in the latter. The key points of the procedure were discussed in detail and the causes and prevention of the disease occurred after injection of sclerotic drugs for hemorrhoids were also discussed.", "Anal fistula is usually treated by either fistulotomy or fistulectomy. We described the routine use of setons to treat anal fistula without any surgery.\n Forty-seven consecutive patients with diagnosed anal fistulae were treated using setons alone.\n The median age of the patients was 41 (range: 18-70). Of the 47 patients, 15 had surgery previously for fistula and perianal abscess. At least two setons were inserted through each fistula. One was tied tightly to function as a cutting seton and this was sequentially tightened by the patient and another was tied loosely for drainage. Of the 47 patients, 33 (70%) had the placement of setons in the clinic without any anaesthesia. The remaining 14 patients had the setons inserted in the operating room, with one patient having a complex anal fistula and 13 patients having perianal abscess requiring drainage at the same time. There were no post procedure complications in the series. Forty-one patients had completed follow up at clinic within a median duration of 15 weeks (range: two to 67 weeks). The fistula was completely healed by this method in 37 patients (78%). The median healing time was nine weeks (range: four to 62 weeks). One patient developed recurrent fistula and was healed after another seton placement. No patient developed any faecal incontinence and all patients were satisfied with this treatment.\n The routine seton method is safe, cheap and effective in the treatment of anal fistula regardless of type. It does not leave an open wound and most patients are satisfied with the treatment.", "Wide varieties of approaches are employed in dealing with low anal fistula. However, the simple method of laying open the fistula tract (fistulotomy) is still considered to be the favored one.\n A modified approach to the procedure of fistulotomy is discussed. This study describes the procedure, which used a technique of radiofrequency surgery, and its outcome in 232 patients with low anal fistula. The patients were followed for a period of 15 months.\n The patients were discharged on the same day as the procedure. The mean period off work was four days. The average healing time recorded was 67 days. Four wound complications in the form of premature closure of the external wound were noted, which required trimming of the edges. Two of these wounds remained unhealed. The recurrence rate was 1.7%.\n In this era when the emphasis is on criteria like the minimization of hospital stay, reduction of postoperative pain, early resumption of work and low and comparable recurrence rates, there is a future for the procedure of radiofrequency fistulotomy.", "Only 4 controlled trials have investigated whether prophylactic abdominal drainage was of value after colonic resection. None have been able to find any statistically significant difference, but the number of patients was small and the beta error risk was high.\n To compare patients who underwent abdominal drainage with those who did not for the rate and severity of complications after elective colonic resection followed immediately by anastomosis of the suprapromontory colon and to compare suction drains with nonsuction drains.\n Between September 1990 and June 1995, 319 patients (135 men and 184 women), whose mean age was 67 years (range, 22-95 years), with carcinoma, benign tumors, or colitis, located anywhere between the ascending and sigmoid colons, were included in the study. Patients were comparable for demographic characteristics, except that there were more patients with ascites in the group that did not undergo abdominal drainage (P<.02).\n After 2 protocol violations, 156 patients were randomized to the abdominal drainage group and 161 to the no abdominal drainage group. All 317 anastomoses were tested for airtightness intraoperatively and repaired if leakage was found (n=71), and all patients with anastomoses received a routine diatrizoate sodium enema to detect infraclinical leakage.\n The postoperative complications possibly influenced by drainage included (1) deep complications for which drainage can lead to early diagnosis, such as generalized or localized peritonitis, intraabdominal hemorrhage, or hematoma; (2) complications believed to be enhanced by drainage, such as an operative wound (an abscess, disruption, or incisional hernia) or pulmonary (microatelectasis) and intestinal obstructions; and (3) complications directly due to the drains, such as ulcerations leading to fistulae, hemorrhages, drainage tract infections, difficulty in removal, intra-abdominal retention, and incisional disruptions. Subsidiary end points were the severity of these complications as assessed by the number of related subsequent operations and deaths.\n Twenty-six patients overall (8%) had postoperative complications possibly influenced by drainage (9% in the group that underwent abdominal drainage and 8% in the group that did not). This difference was not statistically significant (P<.90). One patient had a fistula directly imputable to drainage. There was no difference between suction and nonsuction drainage (P<.90).\n Routine abdominal drainage after colonic resection and immediate anastomosis decreases neither the rate nor the severity of anastomotic leakage. It can, occasionally, be detrimental." ]

[ "18575629", "18568115", "22375972", "17632223", "19884613", "8555958", "15967546", "15991780", "22323576" ]

[ "A vaccine against nicotine for smoking cessation: a randomized controlled trial.", "Extended use of nicotine replacement therapy to maintain smoking cessation in persons with schizophrenia.", "A randomized trial of nicotine-replacement therapy patches in pregnancy.", "A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia.", "A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies.", "Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial.", "Case studies of three pregnant smokers and their use of nicotine replacement therapy.", "A randomised controlled trial to evaluate the efficacy of a nurse-provided intervention for hospitalised smokers.", "Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial." ]

[ "Tobacco dependence is the leading cause of preventable death and disabilities worldwide and nicotine is the main substance responsible for the addiction to tobacco. A vaccine against nicotine was tested in a 6-month randomized, double blind phase II smoking cessation study in 341 smokers with a subsequent 6-month follow-up period.\n 229 subjects were randomized to receive five intramuscular injections of the nicotine vaccine and 112 to receive placebo at monthly intervals. All subjects received individual behavioral smoking cessation counseling. The vaccine was safe, generally well tolerated and highly immunogenic, inducing a 100% antibody responder rate after the first injection. Point prevalence of abstinence at month 2 showed a statistically significant difference between subjects treated with Nicotine-Qbeta (47.2%) and placebo (35.1%) (P = 0.036), but continuous abstinence between months 2 and 6 was not significantly different. However, in subgroup analysis of the per-protocol population, the third of subjects with highest antibody levels showed higher continuous abstinence from month 2 until month 6 (56.6%) than placebo treated participants (31.3%) (OR 2.9; P = 0.004) while medium and low antibody levels did not increase abstinence rates. After 12 month, the difference in continuous abstinence rate between subjects on placebo and those with high antibody response was maintained (difference 20.2%, P = 0.012).\n Whereas Nicotine-Qbeta did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction.\n Swiss Medical Registry 2003DR2327; ClinicalTrials.gov NCT00369616.", "This study was designed to determine the feasibility and efficacy of long-term nicotine replacement therapy (NRT) in helping persons with schizophrenia remain tobacco-free. Fifty smokers with a diagnosis of schizophrenia or schizo-affective disorder and whose symptoms had been stable for at least two months were enrolled in a program providing group support and NRT (patches) in individually adjusted doses set to maintain baseline nicotine intake. All participants attended weekly group support/motivation sessions. Smoking activity was determined by measuring carbon monoxide levels in expired air. Participants who quit tobacco use completely during the first three months were entered into a single-blind phase in which they received either placebo or active nicotine patches for up to six additional months, along with biweekly group sessions. Sixty days into the open-label phase, 66% of the subjects had reduced their use of tobacco by at least 75%. After 90 days of open-label treatment, 18 subjects (36%) were tobacco-free and qualified to enter the six-month, single-blind phase, eight on placebo and nine on active patches. A significantly greater proportion of those on placebo (8 of 8) compared with those on active patches (3 of 9) relapsed prior to completion of the 6-month period. This difference is statistically significant at the p = 0.009 level. The results of this study indicate that long-term use of NRT is feasible and effective for sustained tobacco-free success and may be an important strategy for reducing health risks due to tobacco use in this special population.", "Nicotine-replacement therapy is effective for smoking cessation outside pregnancy and its use is widely recommended during pregnancy. We investigated the efficacy and safety of nicotine patches during pregnancy.\n We recruited participants from seven hospitals in England who were 16 to 50 years of age with pregnancies of 12 to 24 weeks' gestation and who smoked five or more cigarettes per day. Participants received behavioral cessation support and were randomly assigned to 8 weeks of treatment with active nicotine patches (15 mg per 16 hours) or matched placebo patches. The primary outcome was abstinence from the date of smoking cessation until delivery, as validated by measurement of exhaled carbon monoxide or salivary cotinine. Safety was assessed by monitoring for adverse pregnancy and birth outcomes.\n Of 1050 participants, 521 were randomly assigned to nicotine-replacement therapy and 529 to placebo. There was no significant difference in the rate of abstinence from the quit date until delivery between the nicotine-replacement and placebo groups (9.4% and 7.6%, respectively; unadjusted odds ratio with nicotine-replacement therapy, 1.26; 95% confidence interval, 0.82 to 1.96), although the rate was higher at 1 month in the nicotine-replacement group than in the placebo group (21.3% vs. 11.7%). Compliance was low; only 7.2% of women assigned to nicotine-replacement therapy and 2.8% assigned to placebo used patches for more than 1 month. Rates of adverse pregnancy and birth outcomes were similar in the two groups.\n Adding a nicotine patch (15 mg per 16 hours) to behavioral cessation support for women who smoked during pregnancy did not significantly increase the rate of abstinence from smoking until delivery or the risk of adverse pregnancy or birth outcomes. However, low compliance rates substantially limited the assessment of safety. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Current Controlled Trials number, ISRCTN07249128.).", "The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention.", "Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies, yet such evidence is needed to make informed decisions about their clinical use.\n To assess the relative efficacies of 5 smoking cessation pharmacotherapy interventions using placebo-controlled, head-to-head comparisons.\n A randomized, double-blind, placebo-controlled clinical trial.\n Two urban research sites.\n One thousand five hundred four adults who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. Participants were excluded if they reported using any form of tobacco other than cigarettes; current use of bupropion; having a current psychosis or schizophrenia diagnosis; or having medical contraindications for any of the study medications.\n Participants were randomized to 1 of 6 treatment conditions: nicotine lozenge, nicotine patch, sustained-release bupropion, nicotine patch plus nicotine lozenge, bupropion plus nicotine lozenge, or placebo. In addition, all participants received 6 individual counseling sessions.\n Biochemically confirmed 7-day point-prevalence abstinence assessed at 1 week after the quit date (postquit), end of treatment (8 weeks postquit), and 6 months postquit. Other outcomes were initial cessation, number of days to lapse, number of days to relapse, and latency to relapse after the first lapse.\n All pharmacotherapies differed from placebo when examined without protection for multiple comparisons (odds ratios, 1.63-2.34). With such protection, only the nicotine patch plus nicotine lozenge (odds ratio, 2.34, P < .001) produced significantly higher abstinence rates at 6-month postquit than did placebo.\n While the nicotine lozenge, bupropion, and bupropion plus lozenge produced effects that were comparable with those reported in previous research, the nicotine patch plus lozenge produced the greatest benefit relative to placebo for smoking cessation.", "Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation but absolute success rates are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safety and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8-32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO < or = 8 ppm; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.", "To examine the barriers encountered by pregnant women who attempt to stop smoking by highlighting three women who used nicotine patches.\n A randomised-controlled trial of nicotine-replacement therapy (NRT) in the form of patches to test its acceptability for pregnant women. Ethics approval was granted despite NRT being contraindicated in Australia for pregnant women and having a low safety rating (category D) (Australian Drug Evaluation Committee, 1999). Salivary cotinine levels were used to assess nicotine exposure and provide some indicator of NRT safety. All participants were given pregnancy-specific cessation counselling, and the 20 women in the treatment arm were offered nicotine patches (15 mg/16 hr), with the option of weaning to lower strength patches if desired.\n The Women's and Children's Hospital, Adelaide, a public tertiary teaching hospital in South Australia, with almost 4000 births annually.\n 40 'high-risk' pregnant smokers who expressed interest in stopping smoking.\n As has been found in the general population, 'quit' rates with NRT use were low. Only three of the participants in this study, who became abstinent with patch use during pregnancy, were still abstinent at birth. The circumstances of two of these women, and a third woman who used patches to 'control' her smoking despite researcher advice, are detailed here. Only one of the two women 'abstinent at delivery' was still abstinent 3 months after birth, the last contact point of the study.\n Although health providers intuitively regard pregnancy as an appropriate time for women to stop smoking, the stressors during pregnancy seem to militate against cessation. This study does not indicate that use of NRT will provide an easier solution. It may be more fruitful to institute a concerted lifestyle approach with both the woman and her partner (or significant household members), and continue this support and education postnatally if cessation has not been achieved. Health professionals should also support better-targeted public health campaigns and tobacco-control initiatives generally, because, undoubtedly, the social environment is a major determinant of initiation and continuation of smoking.", "Does the provision of a nurse-based intervention lead to smoking cessation in hospital patients?\n At tertiary teaching hospital in Newcastle, Australia, 4,779 eligible (aged 18-80, admitted for at least 24 hours, and able to provide informed consent) and consenting (73.4%) in-patients were recruited into a larger cross-sectional survey. 1,422 (29.7%) smokers (in the last 12 months) were randomly assigned to control (n = 711) or intervention group (n = 711). The brief nurse-delivered intervention incorporated: tailored information, assessment of withdrawal, offer of nicotine replacement therapy, booklets, and a discharge letter. Self-reported cessation at 12 months was validated with CO and salivary cotinine.\n There were no significant differences between groups in self-reported abstinence at three or 12 months post intervention, based on an intention to treat analysis. At three months, self-reported abstinence was 27.3% (I) and 27.5% (C); at 12 months was 18.5% (I) and 20.6% (C). There were no differences in validation of self-report between intervention and control groups at 12 months.\n This brief nurse-provided in-patient intervention did not significantly increase the smoking cessation rates compared with the control group at either three or 12-month follow-up.\n A systematic total quality improvement model of accountable outcome-focused treatment, incorporating assertive physician-led pharmacotherapy, routine assessment and recording of nicotine dependence (ICD 10 coding), in- and outpatient services and engagement from multidisciplinary teams of health professionals may be required to improve treatment modalities for this chronic addictive disorder.", "A nicotine mouth spray has advantages over other acute forms of nicotine replacement therapy, such as a faster uptake of nicotine and faster relief of craving. This multicentre, randomised (2:1), double-blind, placebo-controlled efficacy and safety study evaluated self-reported, carbon monoxide-verified continuous abstinence from smoking from week 2 until weeks 6, 24, and 52 in 479 smokers (≥ 1 cigarette per day) who were treated with either active (n=318) or placebo (n=161) spray for 12 weeks and low-intensity counselling at three smoking cessation clinics in Denmark and Germany. Active treatment yielded significantly higher continuous abstinence rates than placebo from week 2 until week 6 (26.1% versus 16.1%; relative success rate (RR) 1.62, 95% CI 1.09-2.41), week 24 (15.7% versus 6.8%; RR 2.30, 95% CI 1.23-4.30), and week 52 (13.8% versus 5.6%; RR 2.48, 95% CI 1.24-4.94). Most adverse events were mild to moderate, and 9.1% of subjects on active spray withdrew due to adverse events, compared to 7.5% on placebo. The overall rate of treatment-related adverse events was 87.4% with active spray versus 71.4% with placebo spray. Nicotine mouth spray delivered significantly higher 6-, 24- and 52-week continuous abstinence rates than placebo." ]

[ "10212082", "9722255", "11158452", "9024451", "11530870", "12534029", "16765760", "19101390", "8885917" ]

[ "Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome.", "Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.", "A multicenter, randomized open study of early corticosteroid treatment (OSECT) in preterm infants with respiratory illness: comparison of early and late treatment and of dexamethasone and inhaled budesonide.", "Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis.", "The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes.", "[Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study].", "Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial.", "Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial.", "Preterm premature ruptured membranes: a randomized trial of steroids after treatment with antibiotics." ]

[ "To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.\n Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications.\n More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects.\n These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.", "In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.", "To compare early (<3 days) with late (>15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease.\n Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age <30 weeks, postnatal age <72 hours, and need for mechanical ventilation and inspired oxygen concentration >30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (<72 hours) dexamethasone, early budesonide, delayed selective (>15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily.\n There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance.\n Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective.", "To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).\n Prospective, controlled, randomized study.\n Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.\n No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.\n Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly.", "This study was carried out to examine the effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes (PROMs). For this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation) complicated by PROMs were evaluated prospectively during the period January 1997 to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince Zaid). Patients were allocated into two groups; Group 1 included 72 patients treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group 2 which included 67 patients whoreceived no treatment (control group). All women were examined clinically and the diagnosis of PROMs was demonstrated using vaginal speculum, nitrazine paper examination and ultrasonography. All neonates were evaluated clinically, radiologically, and by laboratory investigations. Pearson's Chi-square and Fisher's exact tests were used to assess the significance of differences between the two study groups. Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), and days of hospital stay were significantly reduced in premature infants of the corticosteroid treated women compared with the controls (p<0.04, p<0.04, p<0.04, and p<0.05, respectively). The perinatal mortality was significantly decreased among the corticosteroid treated group in the gestational subgroups 31-32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was statistically a significant factor which resulted in increased perinatal mortality in the control group (p=0.02). Regarding the occurrence of postpartum endometritis there was a statistically significant increase among the corticosteroid treated group compared with the controls (p<0.04). Conclusion: Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a positive influencing effect on premature infants between 31 and 34 weeks of gestation, decreasing significantly the perinatal morbidity and mortality. It should be used with particular relevance to the developing world where surfactant is not available or where neonatal intensive care units are lacking.", "The aim of the study was to determine the feasibility, the cost and the effects of antenatal maternal corticosteroid treatment on preventing respiratory distress syndrome in premature neonates of our population.\n Between January, 1, 1998 and June, 31, 1999, 118 pregnant women at 26-34 weeks' gestation and at a high risk of premature delivery, were prospectively randomized in 2 groups: group 1 received intramusculary 24 mg of betamethasone (12 mg every 24 hours), group 2 didn't receive antenatal corticosteroids. At birth, premature neonates were systematically examined by a neonatologist.\n 131 premature neonates were born (63 from group 1, 68 from group 2). The incidence and the degree of severity of respiratory distress syndrome, appeared substancially reduced (4.8% vs 27.9%) by the use of antenatal corticosteroids. Moreover, neonatal mortality due to respiratory distress syndrome was statistically less in group 1 than in group 2 (22.9% vs 57%). There was no significant difference in the occurrence of maternal or neonatal corticosteroid complications such as infection between treated group and control subjects. We estimated a potential annual savings of 21 thousands tunisian dinars, when the cost implications for antenatal corticosteroid therapy were estimated to 2 thousands tunisian dinars.\n Maternal administration of corticosteroids before preterm delivery results in a decrease in the incidence and severity of respiratory distress syndrome and a decrease in neonatal mortality rate among premature neonates born to treated versus untreated mothers at 26-34 weeks' gestation; added to an annual savings estimated to 21 thousands tunisian dinars.", "The efficacy and safety of repeat doses of prenatal corticosteroids remains uncertain. Our aim was to establish whether repeat prenatal corticosteroids given to women at risk of preterm birth can reduce neonatal morbidity without harm.\n In this hospital-based study, 982 women who remained at risk of preterm birth at less than 32 weeks' gestation, 7 or more days after receiving a first course of prenatal corticosteroids, were randomly assigned to receive a repeat intramuscular dose of either 11.4 mg betamethasone (as Celestone Chronodose), or saline placebo. This was repeated every week the woman remained undelivered, at less than 32 weeks' gestation, and at risk of preterm birth. Primary outcomes were occurrence and severity of neonatal respiratory distress syndrome, use and duration of oxygen and mechanical ventilation, and weight, length, and head circumference at birth and hospital discharge. Statistical analyses were on an intention to treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN48656428.\n Fewer babies exposed to repeat corticosteroids had respiratory distress syndrome (33%vs 41%; relative risk 0.82, 95% CI 0.71-0.95, p=0.01) and fewer had severe lung disease (12%vs 20%; relative risk 0.60, 95% CI 0.46-0.79, p=0.0003) than those in the placebo group. In keeping with these benefits, babies exposed to repeat corticosteroids needed less oxygen therapy (p=0.03), and shorter duration of mechanical ventilation (p=0.01). Mean weight, length, and head circumference at birth and hospital discharge did not differ between treatment groups. Z-scores for weight (p=0.04) and head circumference (p=0.03) at birth were lower in the babies who received repeat corticosteroids although at the time of hospital discharge Z-scores did not differ between treatment groups (p=0.29 for weight, p=0.48 for head circumference).\n Exposure to repeat doses of antenatal corticosteroids reduces neonatal morbidity. Pending long-term outcome results, the short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course.", "One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth.\n 1858 women at 25-32 weeks' gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148.\n Infants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216 g vs 2330 g, p=0.0026), were shorter (44.5 cm vs 45.4 cm, p<0.001), and had a smaller head circumference (31.1 cm vs 31.7 cm, p<0.001).\n Multiple courses of antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes, and are associated with a decreased weight, length, and head circumference at birth. Therefore, this treatment schedule is not recommended.\n Canadian Institutes of Health Research.", "To assess the effectiveness of corticosteroids in patients with preterm premature rupture of membranes (PROM) after treatment with a broad-spectrum antibiotic, ampicillin-sulbactam.\n A randomized clinical trial of corticosteroids in patients with preterm PROM was undertaken after treating these patients for a minimum of 12 hours with ampicillin-sulbactam. No digital vaginal examinations were performed on these patients. Antibiotics were continued for 7 days and the steroids were repeated weekly. No tocolytics were used. The primary outcome measure was the incidence of respiratory distress syndrome (RDS). Secondary outcome measures included latency period and neonatal and maternal infectious morbidity.\n Seventy-seven patients were enrolled and data about their pregnancies were analyzed. No statistically significant difference in latency period was noted (14.7 days in the steroid group, 15.8 days in the no-steroid group). Both neonatal and maternal infectious morbidity were similar. A significant reduction in the incidence of RDS (18.4 versus 43.6%, P = .03) were observed in the steroid group.\n These data suggest that treating preterm PROM patients with a broad-spectrum antibiotic before corticosteroids decreases RDS without apparent adverse sequelae." ]

[ "18490891", "17661342", "16135471", "16462503", "20651011", "21689848", "15022300", "16618589", "10326708" ]

[ "A brief intervention for fatigue management in breast cancer survivors.", "A randomized controlled trial to evaluate the effectiveness of a brief, behaviorally oriented intervention for cancer-related fatigue.", "Randomized controlled trial of an educational intervention for managing fatigue in women receiving adjuvant chemotherapy for early-stage breast cancer.", "Will improvement in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer?", "Cancer-related fatigue and rehabilitation: a randomized controlled multicenter trial comparing physical training combined with cognitive-behavioral therapy with physical training only and with no intervention.", "A randomised controlled trial testing the feasibility and efficacy of a physical activity behavioural change intervention in managing fatigue with gynaecological cancer survivors.", "A randomized clinical trial of energy conservation for patients with cancer-related fatigue.", "Nursing education as an intervention to decrease fatigue perception in oncology patients.", "Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy." ]

[ "The purpose of this randomized control trial was to verify the effectiveness of a brief group intervention that combines stress management psycho-education and physical activity (ie, independent variable) intervention in reducing fatigue and improving energy level, quality of life (mental and physical), fitness (VO 2submax), and emotional distress (ie, dependent variables) in breast cancer survivors. This study applied Lazarus and Folkman stress-coping theoretical framework, as well as Salmon's unifying theory of physical activity. Eighty-seven French-speaking women who had completed their treatments for nonmetastatic breast cancer at a university hospital in Quebec City, Canada, were randomly assigned to either the group intervention (experimental) or the usual-care (control) condition. Data were collected at baseline, postintervention, and at 3-month follow-up. The 4-week group intervention was cofacilitated by 2 nurses. Results showed that participants in the intervention group showed greater improvement in fatigue, energy level, and emotional distress at 3-month follow-up, and physical quality of life at postintervention, compared with the participants in the control group. These results suggest that a brief psycho-educational group intervention focusing on active coping strategies and physical activity is beneficial to cancer survivors after breast cancer treatments.", "It has been shown that nonpharmacologic interventions are effective management techniques for cancer-related fatigue (CRF) in cancer survivors. However, few studies have investigated their effectiveness in patients who are receiving chemotherapy. In this study, the authors tested the effectiveness of a brief behaviorally oriented intervention in reducing CRF and improving physical function and associated distress in individuals who were receiving chemotherapy.\n For this randomized controlled trial, 60 patients with cancer were recruited and received either usual care or the intervention. The intervention was delivered on an individual basis on 3 occasions over a period from 9 weeks to 12 weeks, and the objective of the intervention was to alter fatigue-related thoughts and behavior. Primary outcomes were assessed as follows: CRF using the Visual Analogue Scale-Global Fatigue; physical functioning using the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 Questionnaire, and CRF-associated distress using the Fatigue Outcome Measure. Assessments were made on 4 occasions: at baseline (T0), at the end of chemotherapy (T1), 1 month after chemotherapy (T2), and 9 months after recruitment (T3). Normally distributed data were analyzed using t tests and random-slope/random-intercept mixed models.\n The intervention demonstrated a trend toward improved CRF, although this effect was reduced once confounders had been controlled statistically. There was a significant improvement in physical functioning (coefficient, 10.0; 95% confidence interval, 2.5-17.5; P = .009), and this effect remained once the confounding effects of mood disturbance and comorbid disorders were controlled statistically. No decrease in fatigue-related distress was detected.\n The behaviorally oriented intervention brought about significant improvements in physical functioning, indicated a trend toward improved CRF, but detected no effect for fatigue-related distress.\n (c) 2007 American Cancer Society.", "To evaluate the efficacy of a psychoeducational intervention in improving cancer-related fatigue.\n This randomized controlled trial involved 109 women commencing adjuvant chemotherapy for stage I or II breast cancer in five chemotherapy treatment centers. Intervention group patients received an individualized fatigue education and support program delivered in the clinic and by phone over three 10- to 20-minute sessions 1 week apart. Instruments included a numeric rating scale assessing confidence with managing fatigue; 11-point numeric rating scales measuring fatigue at worst, average, and best; the Functional Assessment of Cancer Therapy-Fatigue and Piper Fatigue Scales; the Cancer Self-Efficacy Scale; the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; and the Hospital Anxiety and Depression Scale. For each outcome, separate analyses of covariance of change scores between baseline (T1) and the three follow-up time points (T2, T3, and T4) were conducted, controlling for the variable's corresponding baseline value.\n Compared with the intervention group, mean difference scores between the baseline (T1) and immediate after the test (T2) assessments increased significantly more for the control group for worst and average fatigue, Functional Assessment of Cancer Therapy-Fatigue, and Piper fatigue severity and interference measures. These differences were not observed between baseline and T3 and T4 assessments. No significant differences were identified for any pre- or post-test change scores for confidence with managing fatigue, cancer self-efficacy, anxiety, depression, or quality of life.\n Preparatory education and support has the potential to assist women to cope with cancer-related fatigue in the short term. However, further research is needed to identify ways to improve the potency and sustainability of psychoeducational interventions for managing cancer-related fatigue.", "Fatigue has a significant impact on the quality of life (QOL) of cancer patients. Recent research has suggested that physical activity can reduce fatigue in patients receiving active cancer treatment. In this project, we examined the impact that participation in a randomized controlled trial of a multidisciplinary intervention designed to impact overall QOL had on fatigue for advanced cancer patients actively receiving treatment.\n Patients with newly diagnosed cancer were randomly assigned to an 8-session structured multidisciplinary intervention or a standard-care arm at the beginning of their course of radiotherapy (RT) designed to impact QOL. Ninety-minute sessions were led by either a psychiatrist or psychologist, collaborating with a nurse, physical therapist, chaplain, or social worker, depending on the session's theme. The fatigue assessments used in this trial included the Linear Analogue Self Assessment (LASA), the Profile of Mood States (POMS), Spielberger's State-Trait Anxiety Inventory (STAI), and the Symptom Distress Scale (SDS).\n There were 115 participants enrolled and the 2 randomization arms were well balanced in terms of baseline characteristics and treatment received except for increased commuting distance for the patients in the intervention arm (P = 0.042). Most of scores indicated less fatigue (higher score) in the standard treatment group, but there were no statistically significant differences found at baseline and weeks 4, 8, and 27 except for SDS at week 8 (P = 0.018) with less patients reporting significant fatigue in the standard treatment arm. For the entire participant population, fatigue levels initially worsened with radiotherapy, stabilized at week 8, and returned to baseline by week 27. Disease site, chemotherapy use, and radiotherapy dose did not have a significant impact on fatigue levels.\n Radiotherapy initially caused a worsening of fatigue but with time fatigue levels returned to baseline. Clinically, this structured multidisciplinary intervention had no impact on fatigue, and there was the suggestion the multiple sessions may have contributed to worse fatigue during active cancer treatment.", "Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial.\n This randomized controlled trial compared the effect on cancer-related fatigue of physical training combined with cognitive behavioral therapy with physical training alone and with no intervention.\n In this multicenter randomized controlled trial, 147 survivors of cancer were randomly assigned to a group that received physical training combined with cognitive-behavioral therapy (PT+CBT group, n=76) or to a group that received physical training alone (PT group, n=71). In addition, a nonintervention control group (WLC group) consisting of 62 survivors of cancer who were on the waiting lists of rehabilitation centers elsewhere was included.\n The study was conducted at 4 rehabilitation centers in the Netherlands.\n All patients were survivors of cancer.\n Physical training consisting of 2 hours of individual training and group sports took place twice weekly, and cognitive-behavioral therapy took place once weekly for 2 hours.\n Fatigue was assessed with the Multidimensional Fatigue Inventory before and immediately after intervention (12 weeks after enrollment). The WLC group completed questionnaires at the same time points.\n Baseline fatigue did not differ significantly among the 3 groups. Over time, levels of fatigue significantly decreased in all domains in all groups, except in mental fatigue in the WLC group. Analyses of variance of postintervention fatigue showed statistically significant group effects on general fatigue, on physical and mental fatigue, and on reduced activation but not on reduced motivation. Compared with the WLC group, the PT group reported significantly greater decline in 4 domains of fatigue, whereas the PT+CBT group reported significantly greater decline in physical fatigue only. No significant differences in decline in fatigue were found between the PT+CBT and PT groups.\n Physical training combined with cognitive-behavioral therapy and physical training alone had significant and beneficial effects on fatigue compared with no intervention. Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training.", "To determine the feasibility and efficacy of a physical activity behavioural change intervention in managing cancer-related fatigue among gynaecological cancer survivors during and post anti-cancer treatments.\n A two arm, single blind, randomised controlled trial was conducted within the Northern Ireland regional Cancer Centre. Thirty three sedentary gynaecological cancer survivors (stage I-III; ≤3 years post diagnosis), experiencing cancer-related fatigue (mild-severe) took part. Participants were randomly assigned to a behavioural change, moderate intensity physical activity intervention (n=16) or a Contact Control group (n=17). The primary outcome was fatigue (Multidimensional Fatigue Symptom Inventory-Short Form and Functional Assessment in Chronic Illness Therapy-Fatigue subscale). Secondary outcomes included quality of life, physical functioning, positive and negative affect, depression, body composition, sleep dysfunction and self-reported physical activity. Feasibility was assessed based on the recruitment rate, programme and physical activity adherence and participants' programme evaluation, including optional focus groups (n=16).\n Twenty five percent of eligible women took part (33/134). Participants were 8.7 (SD=9.1) months post diagnosis, with a mean age of 53 (SD=10.3) years. The majority of the sample had a diagnosis of ovarian (n=12) or endometrial cancer (n=11). Significant differences favouring the intervention group were observed for fatigue at 12 weeks and 6 months follow-up (12 week: mean difference=-11.06; 95% confidence interval (CI)=-21.89 to -0.23; effect size (d)=0.13; p=0.046; 6 month: mean difference=-19.48; 95% CI=-19.67 to -19.15; effect size (d)=0.20; p=0.01). A mean of 10 calls (SD=1.2 calls) were delivered to the Physical Activity Group, and 10 (SD=1.6 calls) to the CC group. The intervention was positively perceived based on exit questionnaire and focus group findings.\n A physical activity behavioural change intervention for gynaecological cancer survivors is feasible in terms of participants' programme adherence and evaluation, and the intervention demonstrates improvements in fatigue. However, confirmation in the form of a larger fully powered RCT is warranted.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "The efficacy of energy conservation and activity management (ECAM) for fatigue reduction and maintenance of functional performance has never been evaluated in adults with cancer who are undergoing treatment.\n A randomized clinical trial compared an ECAM intervention with a control intervention focused on nutrition. Individuals initiating chemotherapy, radiotherapy, or concurrent therapy for cancer were randomized to receive either the semistructured ECAM intervention (n = 200) or the control intervention (n = 196). Participants in each group participated in 3 telephone sessions with an oncology nurse during the first 5 weeks of treatment. Data on fatigue and limitation of functioning were obtained before cancer treatment and at two follow-up points that coincided with times of high fatigue for each type of treatment. The outcomes of interest included perception of fatigue and functional performance.\n A repeated-measures analysis of covariance using the type of cancer treatment as a covariate revealed a significant study group-by-time interaction indicating that the ECAM group experienced a greater decrease in fatigue over time compared with the control group (F(2,544) = 4.5; P = 0.01). The intervention was not associated with changes in overall functional performance.\n Individuals who received the ECAM intervention derived a modest but significant benefit from it. To achieve a more robust clinical benefit from the intervention, it may be necessary to manage other key symptoms in addition to fatigue. Research is needed to examine symptom clusters or combinations associated with negative outcomes as well as combination strategies for symptom management.\n Copyright 2004 American Cancer Society.", "People with cancer have identified fatigue as a major obstacle to normal functioning and a good quality of life. It is a nearly universal symptom for patients undergoing primary antineoplasic therapy or treatment with biologic response modifiers (BRM) and is extremely common in patients with persistent or advanced disease. The aim of the study was to determine whether nursing education decreased the perception of fatigue in patients with colon or gastric cancer. We compared the fatigue level between two groups of patients who received the same treatment and had the same type of cancer (experimental group and control group). We provided an individualised and structured nursing intervention with education to the experimental group. We followed up the fatigue level in both groups with three different measures on the Functional Assessment of Cancer Therapy Fatigue (FACT-F) Scale. After the nursing intervention there was a decrease in the level of fatigue in the experimental group, whereas the group of patients that did not receive this intervention showed an increase in fatigue level along the treatment. The nursing intervention with the individualised education and counselling has provided patients with cancer with an effective tool to manage fatigue.", "Fatigue is a common and often severe problem in cancer patients undergoing chemotherapy. The authors postulated that physical activity training can reduce the intensity of fatigue in this group of patients.\n A group of cancer patients receiving high dose chemotherapy followed by autologous peripheral blood stem cell transplantation (training group; n = 27) followed an exercise program during hospitalization. The program was comprised of biking on an ergometer in the supine position following an interval training pattern for 30 minutes daily. Patients in the control group (n = 32) did not train. Psychologic distress was assessed at hospital admission and discharge with the Profile of Mood States and Symptom Check List 90.\n By the time of hospital discharge, fatigue and somatic complaints had increased significantly in the control group (P for both < 0.01) but not in the training group. Furthermore, by the time of hospital discharge, the training group had a significant improvement in several scores of psychologic distress (obsessive-compulsive traits, fear, interpersonal sensitivity, and phobic anxiety) (P value for all scores < 0.05); this outcome was not observed in the control group.\n The current study found that aerobic exercise can reduce fatigue and improve psychologic distress in cancer patients undergoing chemotherapy." ]

[ "17949458", "15666380", "17697262", "16555338", "16427543", "15723993", "18424367", "15194628", "19092335" ]

[ "The ischemic preconditioning paradox in deceased donor liver transplantation-evidence from a prospective randomized single blind clinical trial.", "Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy.", "Ischemic pre-conditioning in deceased donor liver transplantation: a prospective randomized clinical trial.", "Effect of ischemic preconditioning in whole liver transplantation from deceased donors. A pilot study.", "Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving the caval flow: a randomized prospective study.", "Beneficial effects of ischemic preconditioning in patients undergoing hepatectomy: the role of neutrophils.", "Ischemic preconditioning improves postoperative outcome after liver resections: a randomized controlled study.", "Effects of Pringle manoeuvre and ischaemic preconditioning on haemodynamic stability in patients undergoing elective hepatectomy: a randomized trial.", "A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic." ]

[ "While animal studies show that ischemic preconditioning (IPC) is beneficial in liver transplantation (LT), evidence from few smaller clinical trials is conflicting. From October 2003 to July 2006, 101 deceased donors (DD) were randomized to 10 min IPC (n = 50) or No IPC (n = 51). Primary objective was efficacy of IPC to decrease reperfusion (RP) injury. Both groups had similar donor risk index (DRI) (1.54 vs. 1.57). Aminotransferases on days 1 and 2 were significantly greater (p < 0.05) in IPC recipients. In multivariate analyses, IPC had an independent effect only on day 2 aspartate transferase. Prothrombin time, bilirubin and histological injury were similar in both groups. IPC had no significant effect on plasma TNF-alpha, IL-6 and IL-10 in the donor and TNF-alpha and IL-6 in the recipient. In contrast, IPC recipients had a significant rise in systemic IL-10 levels after RP (p < 0.05) and had fewer moderate/severe rejections within 30 days (p = 0.09). Hospital stay was similar in both groups. One-year patient and graft survival in IPC versus No IPC were 88% versus 78% (p = 0.1) and 86 versus 76% (p = 0.25), respectively. IPC increases RP injury after DDLT, an 'IPC paradox'. Other potential benefits of IPC are limited. IPC may be more effective in combination with other preconditioning regimens.", "Ischemic preconditioning (IPC) has the potential to decrease graft injury and morbidity after liver transplantation. We prospectively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers randomized 1:1 to standard (STD) recovery (N = 28) or IPC (N = 34). Safety was assessed by measurement of heart rate, blood pressure, and visual inspection of abdominal organs during recovery, and efficacy by recipient aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT], both measured in U/L), total bilirubin, and international normalized ratio of prothrombin time (INR) after transplantation. IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion. Recipient median AST, median ALT, and mean INR, in STD vs. IPC were as follows: day 1 AST 696 vs. 841 U/L; day 3 AST 183 vs. 183 U/L; day 1 ALT 444 vs. 764 U/L; day 3 ALT 421 vs. 463 U/L; day 1 INR 1.7 +/- .4 vs. 2.0 +/- .8; and day 3 INR 1.3 +/- .2 vs. 1.4 +/- .3; all P > .05. No instances of nonfunction occurred. The 6-month graft and patient survival STD vs. IPC were 82 vs. 91% and median hospital stay was 10 vs. 8 days; both P > .05. In conclusion, deceased donor livers tolerated 5 minutes of hilar clamping well, but IPC did not decrease graft injury. Further trials with longer periods of preconditioning such as 10 minutes are needed.", "To assess the immediate and long-term effects of ischemic preconditioning (IPC) in deceased donor. liver transplantation (LT), we designed a prospective, randomized controlled trial involving 60 donors: control group (CTL, n = 30) or study group (IPC, n = 30). IPC was induced by 10-min hiliar clamping immediately before recovery of organs. Clinical data and blood and liver samples were obtained in the donor and in the recipient for measurements. IPC significantly improved biochemical markers of liver cell function such as uric acid, hyaluronic acid and Hypoxia-Induced Factor-1 alpha (HIF-1 alpha) levels. Moreover, the degree of apoptosis was significantly lower in the IPC group. On clinical basis, IPC significantly improved the serum aspartate aminotransferase (AST) levels and reduced the need for reoperation in the postoperative period. Moreover, the incidence of primary nonfunction (PNF) was lower in the IPC group, but did not achieve statistical significance. We conclude that 10-min IPC protects against I/R injury in deceased donor LT.", "The effect of ischemic preconditioning (IPC) in orthotopic liver transplantation (OLT) has not yet been clarified. We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors randomly assigned to receive (IPC+ group, n = 23) or not (IPC- group, n = 24) IPC (10-min ischemia + 15-min reperfusion). In 10 cases in the IPC+ group and in 12 in the IPC- group, the expression of inducible nitric oxide synthase (iNOS), neutrophil infiltration, and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies. Median aspartate aminotransferase (AST) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 (398 vs. 1,234 U/L, P = 0.002; and 283 vs. 685 U/L, P = 0.009). Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1, 2, and 3 (333 vs. 934 U/L, P = 0.016; 492 vs. 1,040 U/L, P = 0.008; and 386 vs. 735 U/L, P = 0.022). Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks, incidence of graft nonfunction and graft and patient survival rates were similar between groups. Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups. iNOS was higher postreperfusion vs. prereperfusion in the IPC- group (P = 0.008). Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups (IPC+, P = 0.007; IPC-, P = 0.003). Prereperfusion and postreperfusion apoptosis was minimal in both groups. In conclusion, IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis, but it showed no clinical benefits.\n Copyright 2006 AASLD", "Two randomized prospective studies suggested that ischemic preconditioning (IP) protects the human liver against ischemia-reperfusion injury after hepatectomy performed under continuous clamping of the portal triad. The primary goal of this study was to determine whether IP protects the human liver against ischemia-reperfusion injury after hepatectomy under continuous vascular exclusion with preservation of the caval flow.\n Sixty patients were randomly divided into two groups: with (n=30; preconditioning group) and without (n=30; control group) IP (10 minutes of portal triad clamping and 10 minutes of reperfusion) before major hepatectomy under vascular exclusion of the liver preserving the caval flow. Serum concentrations of aspartate transferase, alanine transferase, glutathione-S-transferase, and bilirubin and prothrombin time were regularly determined until discharge and at 1 month. Morbidity and mortality were determined in both groups.\n Peak postoperative concentrations of aspartate transferase were similar in the groups with and without IP (851 +/- 1,733 IU/L and 427 +/- 166 IU/L respectively, p=0.2). A similar trend toward a higher peak concentration of alanine transferase and glutathione-S-transferase was indeed observed in the preconditioning group compared with the control group. Morbidity and mortality rates and lengths of ICU and hospitalization stays were similar in both groups.\n IP does not improve liver tolerance to ischemia-reperfusion after hepatectomy under vascular exclusion of the liver with preservation of the caval flow. This maneuver does not improve postoperative liver function and does not affect morbidity or mortality rates. The clinical use of IP through 10 minutes of warm ischemia in this technique of hepatectomy is not currently recommended.", "Temporary vascular clampage (Pringle maneuver) during liver surgery can cause ischemia-reperfusion injury. In this process, activation of polymorphonuclear leukocytes (PMNLs) might play a major role. Thus, we investigated the effects of hepatic ischemic preconditioning on PMNL functions.\n Prospective randomized study. Patients who underwent partial liver resection were randomly assigned to 3 groups: group 1 without Pringle maneuver; group 2 with Pringle maneuver, and group 3 with ischemic preconditioning using 10 minutes of ischemia and 10 minutes of reperfusion prior to Pringle maneuver for resection.\n University hospital, Munich, Germany.\n Seventy-five patients underwent hepatic surgery mostly owing to metastasis.\n Perioperative factors for PMNL activation, inflammation, and postoperative hepatocellular integrity.\n Ischemia-reperfusion of the human liver (mean +/- SD time to perform the Pringle maneuver, 35.5 +/- 2.6 minutes) caused (1) a decrease in the number of circulating PMNLs, (2) their intrahepatic sequestration, (3) their systemic activation, and (4) a significant correlation between the degree of their postischemic activation and the postoperative rise in liver enzyme serum levels. In parallel, cytokines with proinflammatory and chemotactic properties were released reaching the highest values when stimulation of PMNLs was most pronounced. When ischemic preconditioning preceded the Pringle maneuver, activation of PMNLs and cytokine plasma levels was reduced as evidenced by the attenuation of superoxide anion production, beta(2)-integrin up-regulation, and interleukin 8 serum concentrations, followed by a significant reduction in serum alanine aminotransferase levels on the first and second postoperative days.\n These results demonstrate in humans that ischemic preconditioning reduces activation of PMNLs elicited by the Pringle maneuver. The down-regulation of potentially cytotoxic functions of PMNLs might be one of yet unknown important pathways that altogether mediate protection by ischemic preconditioning.", "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.", "The Pringle manoeuvre and ischaemic preconditioning are applied to prevent blood loss and ischaemia-reperfusion injury, respectively, during liver surgery. In this prospective clinical trial we report on the intraoperative haemodynamic effects of the Pringle manoeuvre alone or in combination with ischaemic preconditioning.\n Patients (n=68) were assigned randomly to three groups: (i) resection with the Pringle manoeuvre; (ii) with ischaemic preconditioning before the Pringle manoeuvre for resection; (iii) without pedicle clamping.\n Following the Pringle manoeuvre the mean arterial pressure increased transiently, but significantly decreased after unclamping as a result of peripheral vasodilation. Ischaemic preconditioning improved cardiovascular stability by lowering the need for catecholamines after liver reperfusion without affecting the blood sparing benefits of the Pringle manoeuvre. In addition, ischaemic preconditioning protected against reperfusion-induced tissue injury.\n Ischaemic preconditioning provides both better intraoperative haemodynamic stability and anti-ischaemic effects thereby allowing us to take full advantage of blood loss reduction by the Pringle manoeuvre.", "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." ]

[ "7447362", "3046651", "11236113", "8238130", "8238160", "1303479", "2880755", "8116706", "18472878" ]

[ "Prophylactic antibiotics in Caesarean section: effect of a short preoperative course of benzyl penicillin or clindamycin plus gentamicin on postoperative infectious morbidity.", "A double-blind randomized controlled trial on the use of prophylactic antibiotics in patients undergoing elective caesarean section.", "A randomised controlled trial of antibiotic prophylaxis in elective caesarean delivery.", "Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.", "Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture.", "The role of prophylactic antibiotics in caesarean section--a randomised trial.", "Prevention of postoperative infection in cesarean section after rupture of the membranes.", "A prospective, randomized, placebo-controlled trial of penicillin in preterm premature rupture of membranes.", "Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor." ]

[ "The efficacy of a narrow-spectrum (benzyl penicillin) versus broad-spectrum (clindamycin + gentamicin) preoperative antimicrobial prophylaxis was studied in a series of 147 consecutive patients undergoing Caesarean section at the State Maternity Hospital, Helsinki, Finland. Both regimens proved effective in reducing postoperative endometritis: from 33% (19/57 cases) to 6.5% (3/46 cases) in the penicillin treated group, and to 9.5% (4/42 cases) in the clindamycin + gentamicin treated group. The reduction in the incidence of endometritis was not reflected in the duration of hospital stay, which was 7.7 days in the untreated group, 7.8 days in the penicillin treated group, and 7.6 days in the clindamycin + gentamicin treated group. No significant differences between the groups were detected in the incidence of wound infections.", "In a double-blind randomized controlled study 232 patients undergoing elective lower segment caesarean section were randomly allocated to receive a pre-operative prophylactic dose of a combination of crystalline penicillin and chloramphenicol or a placebo. The two groups were comparable in terms of patient characteristics and operation variables. The group receiving antibiotics had significantly fewer febrile and infectious morbid events and thus spent fewer days in hospital than the group receiving the placebo.", "To determine whether prophylactic antibiotic administration using cefoxitin at the time of elective caesarean section significantly reduces infectious morbidity.\n A tertiary teaching hospital in a large urban city in South Africa.\n Women undergoing elective caesarean section.\n A prospective, double-blind randomised placebo-controlled trial.\n Four hundred and eighty women undergoing elective caesarean section had cefoxitin or placebo administration after umbilical cord clamping. Postpartum complications including febrile morbidity, wound infection, endometritis, urinary tract infection, pneumonia and transient postpartum fever were recorded, as were the duration of hospital stay and the need for therapeutic antibiotics.\n Wound infection was the most common complication occurring in 13.3% and 12.5% of women in the placebo and cefoxitin groups, respectively. Prophylactic antibiotics did not decrease febrile morbidity, wound infection, endometritis, urinary tract infection and pneumonia. Women who received cefoxitin stayed on average a day less in hospital than those who received placebo (6.9 vs 7.8 days, risk difference 0.94 CI 1.57 - 0.31 days). Eleven women (4.6%) in the placebo group and eight (3.4%) in the cefoxitin group had microbiological evidence of wound infection. Staphylococcus aureus was the most common pathogen (43%) isolated. Similar proportions in both groups (6.3% placebo and 5.1% cefoxitin) required a course of therapeutic antibiotics.\n Antibiotic prophylaxis with cefoxitin in elective caesarean section did not reduce post-operative infectious morbidity in this double-blind randomised placebo controlled trial.", "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.", "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.", "A prospective randomised controlled study was conducted over a 6 month period on the value of administering prophylactic antibiotics in patients undergoing emergency caesarean section at the Ipoh General Hospital. A total of 222 patients were randomised to receive 24 hours of ampicillin (500 mg per dose), cefoperazone (1 gm per dose) or no antibiotics. In all parameters of patient morbidity, the group receiving cefoperazone showed significantly better results as compared to the group not receiving antibiotics. The ampicillin group also had favourable results but generally not achieving statistical significance. Prophylactic antibiotics appear to be beneficial and consideration should be given to make it a routine in all emergency caesarean sections.", "Patients having a cesarean section more than 6 h after rupture of the membranes constitute a high risk group for postoperative infections. Two such groups were studied. Patients were given either cefuroxime 1.5 g every 8th hour for 24 h followed by cefadroxil 0.5 g twice daily for 6 days or received no medication. The infection rate was significantly reduced in the treatment group as compared to the control group (15% vs. 48%). Non-infected patients had a significantly shorter stay in hospital (8 days vs. 12 days). Combined use of these drugs for prevention of post-cesarean infection has not previously been reported. No side effects of the antibiotic prophylaxis were reported.", "Preterm premature rupture of the fetal membranes is common and frequently results in infectious complications. A prospective, randomized, controlled trial of penicillin versus placebo in preterm premature rupture of membranes is reported. The aim of the study was to determine if prophylactic antibiotics after preterm premature rupture of membranes would reduce infectious complications in the mother or neonate.\n Patients with preterm premature rupture of membranes between 21 and 37 weeks' gestation were randomized into a penicillin group that received 1 million units of benzylpenicillin intravenously every 4 hours followed by 250 mg of potassium phenoxymethyl penicillin (Pen-Vee K, Wyeth-Ayerst) orally twice daily or a placebo group before delivery. Latency period, infectious complications, and neonatal outcomes were studied.\n Patients with preterm premature rupture of membranes who received prophylactic penicillin had fewer infectious complications, including intraamniotic infection and postpartum endometritis (4 vs 11, p < 0.03), without adverse effects on the mother or fetus.\n Prophylactic penicillin in patients with preterm premature rupture of membranes reduces maternal infectious complications without adversely affecting the mother or newborn.", "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." ]

[ "12193488", "3524668", "9252001", "8110580", "3266072", "8379864", "3538985", "7917733", "9758071" ]

[ "Iliohypogastric-ilioinguinal peripheral nerve block for post-Cesarean delivery analgesia decreases morphine use but not opioid-related side effects.", "Pain relief in labour using transcutaneous electrical nerve stimulation (TENS). A TENS/TENS placebo controlled study in two parity groups.", "Transcutaneous nerve stimulation (TENS) during the first stage of labour: a randomized clinical trial.", "Comparison of the effectiveness of bilateral ilioinguinal nerve block and wound infiltration for postoperative analgesia after caesarean section.", "An evaluation of transcutaneous electrical nerve stimulation for pain relief in labour.", "Abdominal nerve blockade for postoperative analgesia after caesarean section.", "Transcutaneous electrical nerve stimulation following appendicectomy: the placebo effect.", "Multimodal analgesia before thoracic surgery does not reduce postoperative pain.", "Analysis of peak magnitude and duration of analgesia produced by local anesthetics injected into sympathetic ganglia of complex regional pain syndrome patients." ]

[ "To examine if ilioinguinal-iliohypogastric nerve block could reduce the need for post-Cesarean delivery morphine analgesia and thus reduce the incidence of opioid related adverse-effects.\n A multi-level technique for performing the nerve block with bupivacaine was developed and then utilized in this two-part study. Part one was a retrospective assessment of Cesarean delivery patients with and without ilioinguinal-iliohypogastric blocks to determine if the technique reduced patient controlled analgesia morphine use and thus would warrant further study. The second phase was a randomized double-blind placebo-controlled trial to compare post-Cesarean morphine use and the appearance of opioid-related side effects between the anesthetic and placebo-injected groups.\n Both phases demonstrated that our method of ilioinguinal-iliohypogastric nerve block significantly reduced the amount of iv morphine used by patients during the 24 hr following Cesarean delivery. In the retrospective assessment, morphine use was 49 +/- 30 mg in the block group vs 79 +/- 25 mg in the no block group (P = 0.0063). For the prospective trial, patients who received nerve blocks with bupivacaine had a similar result, self-administering 48 +/- 27 mg of morphine over 24 hr compared to 67 +/- 28 mg administered by patients who received infiltrations of saline. However, despite the significant decrease in morphine use, there was no reduction in opioid-related adverse effects: the incidences of nausea were 41% and 46% (P = 0.70) and for itching were 79% and 63% (P = 0.25) in the placebo and nerve block groups, respectively.\n A multi-level ilioinguinal-iliohypogastric nerve block technique can reduce the amount of systemic morphine required to control post-Cesarean delivery pain but this reduction was not associated with a reduction of opioid related adverse effects in our study group.", "The analgesic effects of transcutaneous electrical nerve stimulation (TENS) in labour and effects on outcome were investigated in a double-blind TENS/TENS placebo controlled trial in 100 primigravidae and 50 women in their third labour. There were no differences between the TENS and the TENS placebo users in terms of pain concept or relief, and only 12 and 13% of primigravidae and 48 and 39% of the para 2 women completed labour without requiring other analgesia in their respective groups. The primigravidae who used either TENS or TENS placebo alone had shorter labours than those who required further analgesia. Although the outcome of labour for mother and infant were similar in the two groups, there was a higher operative delivery rate in women who also had epidural analgesia. There were highly significant differences between the TENS and the TENS placebo users in terms of favourable and unfavourable comments by the mothers and the midwives at 1 and 24 h after delivery. The evident consumer satisfaction for TENS suggests TENS has a part to play in analgesia in labour but the equivocal findings in terms of factors associated with pain relief points to the need for apparatus more specifically designed to cope with the special characteristics of the pain of labour.", "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.", "We have studied the effects of bilateral ilioinguinal nerve block and wound infiltration with 0.5% bupivacaine on postoperative pain and analgesic requirements in 62 patients undergoing Caesarean section under general anaesthesia. A control group received no local anaesthetic supplementation. Both ilioinguinal block and wound infiltration reduced significantly the pain scores and analgesic requirements in the immediate postoperative period (P < 0.05). The differences in pain scores and analgesic requirements between the study groups were not statistically significant (P > 0.05).", "The effectiveness of transcutaneous nerve stimulation (TENS) for pain relief in labour was evaluated by randomizing 280 patients in early labour into 2 groups. Inoperative sham machines were applied to patients in the control group and active units to those in the test group. Neither patients nor attending labour ward staff were aware of which group the patient was in. The intensity of low back pain and abdominal pain was assessed by the patient each hour on a visual analogue pain scale. Each patient served as her own control by switching off the machine for 2 contractions every hour and then recording the intensity of pain. The amount of conventional analgesia each patient received was recorded by labour ward staff. There was no difference in the intensity of pain recorded by each group. Nor was there any difference between the 2 groups in the change of pain experienced when the machine was switched off. Moreover there was no difference in the amount of other analgesia required. Some differences were found when those with little low back pain were excluded from the study. We conclude that TENS is ineffective as a routine method of pain relief in labour. It is likely to benefit only those with severe back pain and then only to a modest degree.", "A prospective study of blocking T10-L1 with local anaesthetic, bilaterally in 30 patients undergoing caesarean section under general anaesthesia has been shown to provide effective postoperative analgesia thus requiring significantly less narcotics (mean 66.6 mg of pethidine) compared to the 30 patients in the control group (mean 163 mg of pethidine). A cocktail of 0.5% of bupivacaine with adrenaline and xylocaine 1% produced analgesia for the duration ranging from 8 to 12 hours (mean 8.4 hours). Patients with abdominal field block were awake, alert and comfortable during the immediate postoperative period. They were pain-free sufficiently to put the babies to the breast early and frequently.", "A controlled trial was undertaken to compare the efficacy of transcutaneous electrical nerve stimulation (TENS) with standard intramuscular opiate analgesia in the management of postoperative pain following appendicectomy. Consecutive patients undergoing emergency appendicectomy were randomised into control, sham TENS and active TENS groups. There was a significant decrease in pain severity and analgesic intake in both active and sham TENS groups when compared with the control group (P less than 0.01). No difference was demonstrated in pain severity between active and sham TENS groups but the active TENS group required slightly less analgesia. These results suggest that the major benefit of TENS in the postappendicectomy patient is due to its 'placebo effect' and its use in this situation cannot be recommended.", "Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain.", "Pain-relieving effects of lidocaine/bupivicaine local anesthetic (LA) and saline (S) block of sympathetic ganglia (stellate block, 4 patients; lumbar sympathetic block, 3 patients) were compared in 7 complex regional pain syndrome (CRPS) patients on a double-blind crossover basis to evaluate the diagnostic and therapeutic value of local anesthetic sympathetic blocks.\n Patients rated their pain on a visual analog scale before and after blocks and were tested for mechanical allodynia one-half hour after blocks. Thereafter, they rated their pain intensity in diaries four times a day for 7 days. Each patient received two blocks, S and LA, and served as his own control.\n Both S and LA injections of sympathetic ganglia produced large reductions in pain intensity in 6 of 7 patients 30 minutes after block. These large reductions were accompanied by the reversal of mechanical allodynia in both S and LA. The mean difference between initial peak reduction in pain intensity produced by saline (68.7%) and active local anesthetic (74.4%) did not approach statistical significance. In striking contrast, the mean duration of pain relief was reliably longer in the case of LA (3 days, 18 hours) as compared with S ( 19.9 hours), a difference that occurred in all 7 patients. In a larger sample of 41 CRPS patients, signs of sympathetic efferent blockade, including Homer' s syndrome or skin surface temperature change, were not predictive of initial peak magnitude of pain relief from sympathetic blockade but were predictive of duration of pain reduction.\n The combination of these results provides evidence that duration of pain relief is affected by injection of local anesthetics into sympathetic ganglia. These results indicate that both magnitude and duration of pain reduction should be closely monitored to provide optimal efficacy in procedures that use local anesthetics to treat CRPS." ]

[ "3044868", "16241013", "3552457", "10440619", "1544291", "10383546", "17303970", "7644238", "9831059" ]

[ "Analgesic effect of aspirin, mefenamic acid and their combination in post-operative oral surgery pain.", "Randomized controlled trial of mefenamic acid vs paracervical block for relief of pain for outpatient uterine curettage.", "Comparison of two formulations of lignocaine spray with mefenamic acid in the relief of post-episiotomy pain: a placebo-controlled study.", "Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain: a randomized, controlled trial.", "Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain.", "The efficacy of a novel adenosine agonist (WAG 994) in postoperative dental pain.", "MK-0703 (a cyclooxygenase-2 inhibitor) in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study.", "Analgesic efficacy and safety of single-dose intramuscular ketorolac for postoperative pain management in children following tonsillectomy.", "The comparative efficacy of aceclofenac and ibuprofen in postoperative pain after third molar surgery." ]

[ "A double-blind randomized single dose study of the analgesic effects of 650 mg aspirin, 250 mg mefenamic acid, the combination of 650 mg aspirin and 250 mg mefenamic acid and placebo on 120 patients with pain following oral surgery was conducted. Patients evaluated their pain intensity and extent of pain relief at 1, 2, 3 and 4 h after drug administration. For most parameters, including the sum of the pain intensity differences and the sum of the hourly pain relief scores, each of the drugs was more effective than placebo. Aspirin-mefenamic acid in combination was more effective than both drugs alone, and aspirin and mefenamic acid alone were equally effective for most of the analgesic variables.", "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.", "The analgesic effectiveness of aqueous and alcoholic formulations of lignocaine (5%) spray was compared with that of mefenamic acid (500 mg) or placebo in a double-blind study in 103 primiparous patients complaining of moderate or severe perineal pain associated with episiotomy. The results, assessed after a single dose, showed that the aqueous lignocaine formulation provided a level of pain relief superior to that obtained with the alcoholic formulation or placebo, and similar to that obtained with mefenamic acid.", "Previous data have suggested that rofecoxib, a cyclooxygenase (COX)-2-specific inhibitor, had analgesic effects similar to those of the nonsteroidal anti-inflammatory drugs when tested in the post-dental surgery pain model. The objective of this parallel-group, double-masked, randomized, placebo- and active comparator-controlled clinical trial was to assess more fully the analgesic efficacy of rofecoxib in the treatment of postoperative dental pain. After dental surgery, 151 patients (50.3% women; mean age, 18.3 years; 93.4% white) experiencing moderate-to-severe pain were to receive a single dose of placebo, rofecoxib 50 mg, or ibuprofen 400 mg. Analgesic efficacy was assessed for up to 24 hours postdose using self-administered questionnaires. Tolerability was assessed using spontaneous reports of adverse experiences, physical findings, and laboratory measurements. The results of this study demonstrated that rofecoxib 50 mg was more effective than placebo on all measures of analgesic efficacy. Rofecoxib 50 mg exhibited overall analgesic effects, onset of analgesia, and peak analgesic effects that were not significantly different from those of ibuprofen 400 mg, with a significantly longer duration of action (P < 0.05). We concluded that rofecoxib was efficacious in the treatment of postoperative dental pain and that COX-2-derived prostanoids play a role in treatment of the pain associated with dental surgery.", "We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti-inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose-response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action.", "To determine the comparative efficacy of a new novel adenosine agonist (WAG 994) in postoperative pain after third molar surgery.\n One hundred and twenty-two patients with postoperative pain after third molar surgery were randomised in a placebo double-blind trial with an active control group. In the early postoperative period patients received either a single dose of WAG 994 1 mg, ibuprofen 400 mg or matched placebos. Pain intensity score was recorded on serial visual analogue scales over a 6 h investigation period. Similarly, pain relief was completed on a 4 point categorical scale at each evaluation point. Patients had access to escape analgesic and if these were taken, the time and dosage were recorded. A sparse sampling technique was used to investigate the relationship between analgesic effects and plasma concentrations of WAG 994.\n All three treatment groups were matched for various demographic variables. For all efficacy measures, WAG 994 was not significantly different from placebo (P >0.05), whereas ibuprofen 400 mg was significantly superior to placebo (P<0.001). No significant relationships (P<0.05) were found between WAG 994 pharmacokinetic variables and efficacy measures. Conclusion WAG 994, an adenosine agonist, did not show efficacy in the management of postoperative pain after third molar surgery. Although this pain responds well to nonsteroidal anti-inflammatory drugs, it appears to be resistant to compounds that interact with purinergic receptors.", "MK-0703 is a selective cyclooxygenase-2 inhibitor investigated for the treatment of acute pain and inflammation. The purpose of this single-dose, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was to compare MK-0703 12.5, 50, and 100 mg with ibuprofen 400 mg or placebo in patients who experienced moderate to severe pain after surgical removal of at least 2 third molars. Overall analgesic effect, duration of analgesic effect, time to onset of analgesic effect, peak analgesic effect, and tolerability were assessed over a 24-hour postdose period. The primary endpoint of this study was total pain relief over 8 hours postdose. The study included 121 patients (mean age, 23 yr); 16, 31, 28, 31, and 15 patients enrolled in the placebo, MK-0703 12.5 mg, MK-0703 50 mg, MK-0703 100 mg, and ibuprofen 400 mg groups, respectively. Both MK-0703 50 and 100 mg were significantly more effective than placebo for all endpoints (P < 0.01) and comparable with ibuprofen 400 mg. The onset of analgesic effect in the MK-0703 50 mg and 100 mg and ibuprofen 400 mg groups did not differ significantly from each other (P > 0.20). MK-0703 was generally well tolerated in single doses up to 100 mg. In summary, MK-0703 50 and 100 mg were efficacious in the treatment of postoperative dental pain and were indistinguishable from the active comparator, ibuprofen 400 mg.", "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)", "The aim of the present placebo-controlled, double-blind study was to evaluate the comparative efficacy of single doses of aceclofenac 150 mg and ibuprofen 400 mg in 217 patients with postoperative pain after third molar surgery. Outcome of primary efficacy was judged by overall assessment of the area under the curve (AUC) of graphs for pain intensity (AUC pain) pain relief (AUC relief), both measured from serial visual analogue scales over a 6 h investigation period. Other measures of efficacy included the rate of pain reduction in the first hour, the number of patients who took 'escape' analgesics and the time before they did, and an overall assessment of pain relief score on a five-point categorical scale. Ibuprofen 400 mg was significantly superior to placebo for pain relief (P < 0.01), degree of pain reduction in the first hour (P = 0.005), and the number of patients who required escape analgesia (P < 0.001), and the time before they did (P < 0.001). The outcome for patients treated with aceclofenac 150 mg was not significantly different from that of patients treated with placebo (P > 0.05). A single dose of ibuprofen 400 mg provided significant pain relief in the early postoperative period after third molar surgery, whereas a single dose of aceclofenac 150 mg was not effective in the management of postoperative pain after this operation." ]

[ "21125215", "10092916", "7710151", "2569600", "12040756", "12362006", "2950392", "18260980", "7631339" ]

[ "Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials.", "Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial.", "Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen.", "Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication.", "Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain.", "Hyperbaric oxygen for acute carbon monoxide poisoning.", "[Ineffectiveness of hyperbaric oxygen therapy in multiple sclerosis. A randomized placebo-controlled double-blind study].", "[Long-term results of the use of hyperbaric oxygenation in patients with acute myocardial infarction].", "Hyperbaric oxygen in the treatment of acute ischemic stroke. A double-blind pilot study." ]

[ "Although hyperbaric oxygen therapy (HBO) is broadly used for carbon monoxide (CO) poisoning, its efficacy and practical modalities remain controversial.\n To assess HBO in patients poisoned with CO.\n Two prospective randomized trial on two parallel groups.\n Critical Care Unit, Raymond Poincaré Hospital, Garches, France.\n Three hundred eighty-five patients with acute domestic CO poisoning.\n Patients with transient loss of consciousness (trial A, n = 179) were randomized to either 6 h of normobaric oxygen therapy (NBO; arm A0, n = 86) or 4 h of NBO plus one HBO session (arm A1, n = 93). Patients with initial coma (trial B, n = 206) were randomized to either 4 h of NBO plus one HBO session (arm B1, n = 101) or 4 h of NBO plus two 2 HBO sessions (arm B2, n = 105). PRIMARY ENDPOINT: Proportion of patients with complete recovery at 1 month.\n In trial A, there was no evidence for a difference in 1-month complete recovery rates with and without HBO [58% compared to 61%; unadjusted odds ratio, 0.90 (95% CI, 0.47-1.71)]. In trial B, complete recovery rates were significantly lower with two than with one HBO session [47% compared to 68%; unadjusted odds ratio, 0.42 (CI, 0.23-0.79)].\n In patients with transient loss of consciousness, there was no evidence of superiority of HBO over NBO. In comatose patients, two HBO sessions were associated with worse outcomes than one HBO session.", "To assess neurological sequelae in patients with all grades of carbon monoxide (CO) poisoning after treatment with hyperbaric oxygen (HBO) and normobaric oxygen (NBO).\n Randomised controlled double-blind trial, including an extended series of neuropsychological tests and sham treatments in a multiplace hyperbaric chamber for patients treated with NBO.\n The multiplace hyperbaric chamber at the Alfred Hospital, a university-attached quarternary referral centre in Melbourne providing the only hyperbaric service in the State of Victoria.\n All patients referred with CO poisoning between 1 September 1993 and 30 December 1995, irrespective of severity of poisoning. Pregnant women, children, burns victims and those refusing consent were excluded.\n Daily 100-minute treatments with 100% oxygen in a hyperbaric chamber--60 minutes at 2.8 atmospheres absolute for the HBO group and at 1.0 atmosphere absolute for the NBO group--for three days (or for six days for patients who were clinically abnormal or had poor neuropsychological outcome after three treatments). Both groups received continuous high flow oxygen between treatments.\n Neuropsychological performance at completion of treatment, and at one month where possible.\n More patients in the HBO group required additional treatments (28% v. 15%, P = 0.01 for all patients; 35% v. 13%, P = 0.001 for severely poisoned patients). HBO patients had a worse outcome in the learning test at completion of treatment (P = 0.01 for all patients; P = 0.005 for severely poisoned patients) and a greater number of abnormal test results at completion of treatment (P = 0.02 for all patients; P = 0.008 for severely poisoned patients). A greater percentage of severely poisoned patients in the HBO group had a poor outcome at completion of treatment (P = 0.03). Delayed neurological sequelae were restricted to HBO patients (P = 0.03). No outcome measure was worse in the NBO group.\n In this trial, in which both groups received high doses of oxygen, HBO therapy did not benefit, and may have worsened, the outcome. We cannot recommend its use in CO poisoning.", "Carbon monoxide (CO) poisoning is a major clinical problem. The risk of morbidity and the most effective treatment have not been clearly established. We measured the incidence of delayed neurologic sequelae (DNS) in a group of patients acutely poisoned with CO and tested the null hypothesis that the incidence would not be affected by treatment with hyperbaric oxygen (HBO).\n We conducted a prospective, randomized study in patients with mild to moderate CO poisoning who presented within 6 hours. Patients had no history of loss of consciousness or cardiac instability.\n The incidence of DNS was compared between groups treated with ambient pressure 100% oxygen or HBO (2.8 ATA for 30 minutes followed by 2.0 ATA oxygen for 90 minutes). DNS were defined as development of new symptoms after oxygen treatment plus deterioration on one or more subtests of a standardized neuropsychologic screening battery.\n In 7 of 30 patients (23%), DNS developed after treatment with ambient-pressure oxygen, whereas no sequelae developed in 30 patients after HBO treatment (P < .05). DNS occurred 6 +/- 1 (mean +/- SE) days after poisoning and persisted 41 +/- 8 days. At follow-up 4 weeks after poisoning, patients who had been treated with ambient pressure oxygen and had not sustained DNS exhibited a worse mean score on one subtest, Trail Making, compared with the group treated with HBO and with a control group matched according to age and education level. There were no differences in scores between the control group and the hyperbaric oxygen group.\n DNS after CO poisoning cannot be predicted on the basis of a patient's clinical history or CO level. HBO treatment decreased the incidence of DNS after CO poisoning.", "The value of hyperbaric oxygen in the treatment of acute carbon monoxide intoxication was assessed in 629 adults who had been poisoned at home in the 12 h before admission to hospital. In patients without initial impairment of consciousness (group A) the effect of 6 h of normobaric oxygen (NBO) (group A0, n = 170) was compared with that of 2 h of hyperbaric oxygen (HBO) at 2 atmospheres absolute (ATA) plus 4 h NBO (group A1, n = 173). At the 1 month follow-up 66% of A0 and 68% of A1 patients had recovered. In patients with initial impairment of consciousness the effect of one session of HBO (group B1, n = 145) was compared with that of two sessions (group B2, n = 141); all group B patients also received 4 h of NBO. At 1 month of follow-up 54% group B1 and 52% group B2 patients had recovered. The 7 patients left with neuropsychiatric sequelae (3 B1, 4 B2) and the 4 who died (2 B1, 2 B2) had all presented with coma. HBO was not useful in patients who did not lose consciousness during carbon monoxide intoxication, irrespective of their carboxyhaemoglobin level, nor were two sessions of HBO in patients who sustained only a brief loss of consciousness. The prognosis is poorest for those presenting with coma; the trial needs to be pursued in this group of patients until the power of the study is sufficient to demonstrate the value or otherwise of HBO.", "Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain.\n Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neuropsychological test at 3 months without treatment in that period and started HBO thereafter.\n All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance.\n HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement.", "Patients with acute carbon monoxide poisoning commonly have cognitive sequelae. We conducted a double-blind, randomized trial to evaluate the effect of hyperbaric-oxygen treatment on such cognitive sequelae.\n We randomly assigned patients with symptomatic acute carbon monoxide poisoning in equal proportions to three chamber sessions within a 24-hour period, consisting of either three hyperbaric-oxygen treatments or one normobaric-oxygen treatment plus two sessions of exposure to normobaric room air. Oxygen treatments were administered from a high-flow reservoir through a face mask that prevented rebreathing or by endotracheal tube. Neuropsychological tests were administered immediately after chamber sessions 1 and 3, and 2 weeks, 6 weeks, 6 months, and 12 months after enrollment. The primary outcome was cognitive sequelae six weeks after carbon monoxide poisoning.\n The trial was stopped after the third of four scheduled interim analyses, at which point there were 76 patients in each group. Cognitive sequelae at six weeks were less frequent in the hyperbaric-oxygen group (19 of 76 [25.0 percent]) than in the normobaric-oxygen group (35 of 76 [46.1 percent], P=0.007), even after adjustment for cerebellar dysfunction and for stratification variables (adjusted odds ratio, 0.45 [95 percent confidence interval, 0.22 to 0.92]; P=0.03). The presence of cerebellar dysfunction before treatment was associated with the occurrence of cognitive sequelae (odds ratio, 5.71 [95 percent confidence interval, 1.69 to 19.31]; P=0.005) and was more frequent in the normobaric-oxygen group (15 percent vs. 4 percent, P=0.03). Cognitive sequelae were less frequent in the hyperbaric-oxygen group at 12 months, according to the intention-to-treat analysis (P=0.04).\n Three hyperbaric-oxygen treatments within a 24-hour period appeared to reduce the risk of cognitive sequelae 6 weeks and 12 months after acute carbon monoxide poisoning.\n Copyright 2002 Massachusetts Medical Society", "Seventeen patients with definite and progressive multiple sclerosis entered a double-blind randomized placebo-controlled therapeutic trial of hyperbaric oxygen (HBO). Exposure in monoplace chamber was 90 minutes long each time, 5 days a week, for 4 weeks. The treatment and placebo groups received 100% oxygen at 1.5 bar constant pressure or normal air at 0.1-0.2 bar, respectively. The clinical status of the patients in both groups were compared until one year after treatment. There was no benefit of HBO versus placebo according to the Kurtzke disability status scale. A lesser proportion of patients with deterioration of bowel/bladder function 12 months after therapy was the only benefit of HBO versus placebo according to Kurtzke functional systems scales. On the whole however, HBO is useless in the management of progressive forms of multiple sclerosis.", "Effect of hyperbaric oxygenation (HBO) on mortality and rate of development of reinfarctions during 24 month follow-up was studied in 129 otherwise conventionally treated patients with acute myocardial infarction (AMI). These patients were randomly divided into control (n=65) and intervention (n=64) groups. In the latter group treatment was supplemented with course of HBO. This course consisted of 6 HBO sessions in a single-place chamber (isopression for 40 min at working pressure 0.03 MPa o.d.) starting from day 4 - 6 of the disease. The use of HBO in combination with traditional course of drug treatment significantly reduced rate of reinfarctions (control group - 19%, intervention group - 5.3%, p < 0.05) and increased survival (control group 86.2%, intervention group 94.7%) during 2 years after hospital discharge. Maximal effect on survival was seen during first 0.5 years (91.4 and 100% in control and intervention groups, respectively, p=0.05).", "The effects of hyperbaric oxygen (HBO) therapy on humans are uncertain. Our study aims first to outline the practical aspects and the safety of HBO treatment and then to evaluate the effect of HBO on long-term disability.\n Patients who experienced middle cerebral artery occlusion and were seen within 24 hours of onset were randomized to receive either active (HBO) or sham (air) treatment. The HBO patients were exposed daily to 40 minutes at 1.5 atmospheres absolute for a total of 10 dives. We used the Orgogozo scale to establish a pretreatment functional level. Changes in the Orgogozo scale score at 6 months and 1 year after therapy were used to assess the therapeutic efficacy of HBO. In addition, we used the Rankin scale and our own 10-point scale to assess long term-disability at 6 months and 1 year. Two sample t tests and 95% confidence intervals were used to compare the mean differences between the two treatment groups. Student's two-tailed test was used to compare the differences between pretherapeutic and posttherapeutic scores at 6 months and 1 year in the two treatment groups.\n Over the 3 years of study enrollment, 34 patients were randomized, 17 to hyperbaric treatment with air and 17 to hyperbaric treatment with 100% oxygen. There was no significant difference at inclusion between groups regarding age, time from stroke onset to randomization, and Orgogozo scale scores. Neurological deterioration occurred during the first week in 4 patients in the sham group, 3 of whom died; this worsening was clearly related to the ischemic damage. Treatment was also discontinued for 3 patients in the HBO group who experienced myocardial infarction, a worsening related to the ischemic process, and claustrophobia. Therefore, 27 patients (13 in the sham group and 14 in the HBO group) completed a full course of therapy. The mean score of the HBO group was significantly better on the Orgogozo scale at 1 year (P < .02). However, the difference at 1 year between pretherapeutic and posttherapeutic scores was not significantly different in the two groups (P < .16). Moreover, no statistically significant improvement was observed in the HBO group at 6 months and 1 year according to Rankin score (P < .78) and our own 10-point scale (P < .50).\n Although the small number of patients in each group precludes any conclusion regarding the potential deleterious effect of HBO, we did not observe the major side effects usually related to HBO. Accordingly, it can be assumed that hyperbaric oxygen might be safe. We hypothesize that HBO might improve outcome after stroke, as we detected an outcome trend favoring HBO therapy. A large randomized trial might be required to address the efficacy of this therapy." ]

[ "11890637", "15113965", "10721929", "11053509", "12164031", "12354473", "17928808", "11814373", "8816034" ]

[ "Will iron supplementation given during menstruation improve iron status better than weekly supplementation?", "Daily iron supplementation is more efficacious than twice weekly iron supplementation for the treatment of childhood anemia in western Kenya.", "Efficacy and acceptability of two iron supplementation schedules in adolescent school girls in Lima, Peru.", "Daily iron supplementation is more effective than twice weekly iron supplementation in pregnant women in Pakistan in a randomized double-blind clinical trial.", "Intermittent oral iron supplementation during pregnancy.", "Intermittent administration of iron and sulfadoxine-pyrimethamine to control anaemia in Kenyan children: a randomised controlled trial.", "The effect of weekly iron and vitamin A supplementation on hemoglobin levels and iron status in adolescent schoolgirls in western Kenya.", "Weekly vs daily iron and folic acid supplementation in adolescent Nepalese girls.", "Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani Division, Tanzania." ]

[ "To investigate the efficacy of two different iron supplements administered either on a weekly basis or during menstruation, a 16-week community experimental study was carried out among postmenarcheal female adolescent students in Kupang, East Nusa Tenggara, Indonesia. Forty eight students received a placebo tablet weekly, 48 other students got an iron tablet weekly and 41 students took an iron tablet for four consecutive days during their menstruation cycle. All subjects were given deworming tablets before supplementation. Haemoglobin, serum ferritin, height, weight, mid-upper arm circumference and dietary intake were assessed before and after intervention. The supplementation contributed to a significant improvement in the iron status of the intervention groups compared to the placebo group (P < 0.05). In the menstruation group, the haemoglobin concentrations of the anaemic subjects improved significantly (P < 0.05) while for the non-anaemic subjects, serum ferritin concentrations also increased significantly (P < 0.05). In the weekly group for anaemic and nonanaemic subjects, there was a significant increase in both haemoglobin and serum ferritin concentrations (P < 0.05). This study revealed that weekly supplementation of iron tablets continued for 16 weeks contributed a higher improvement to haemoglobin concentration, compared with supplementing iron tablets for four consecutive days during menstruation for four menstrual cycles. This suggests that weekly iron supplementation is preferable.", "A recent meta-analysis of 14 clinical trials indicated that daily compared with intermittent iron supplementation resulted in significantly greater hematological improvement in pregnant women. No such definitive beneficial effect was demonstrated in preschool children. We compared the efficacy of daily and twice weekly iron supplementation for 6 wk under supervised and unsupervised conditions in the treatment of mild and moderate anemia [hemoglobin (Hb) 50-109 g/L] in children aged 2-59 mo living in a malaria-endemic area of western Kenya. The study was a cluster-randomized trial using a factorial design; participants were aware of the treatment assigned. All children (n = 1049) were administered a single dose of sulfadoxine-pyrimethamine at enrollment followed by 6 wk of daily supervised iron supplementation [3-6 mg/(kg.d)], twice weekly supervised iron supplementation [6-12 mg/(kg.wk)], daily unsupervised iron supplementation, or twice weekly unsupervised iron supplementation. In the supervised groups, Hb concentrations at 6 and 12 wk (6 wk postsupplementation) were significantly higher in children given iron daily rather than twice weekly [mean (95% CI) difference at 6-wk: 4.2 g/L (2.1, 6.4); 12-wk: 4.4 g/L (1.8, 7.0)]. Among the unsupervised groups, Hb concentrations were not different at 6 wk [mean (95% CI) difference: 0.86 g/L (-1.4, 3.1)], but significantly higher at 12 wk for those assigned daily iron [mean (95% CI) difference: 3.4 g/L (0.79, 6.0), P = 0.02]. In this malarious area and after initial antimalarial treatment, 6 wk of daily iron supplementation results in better hematological responses than twice weekly iron supplementation in the treatment of anemia in preschool children, regardless of whether adherence can be ensured.", "To assess the efficacy and acceptability of a daily and intermittent iron supplementation, a double-blind, placebo-controlled trial was conducted in a public school located in periurban Lima, Peru. Adolescent girls (n = 312), 12-18 y old, were randomly assigned to one of the following three groups: 1) 60 mg iron as ferrous sulfate daily from Monday to Friday; 2) 60 mg iron as ferrous sulfate 2 d/wk and 3 d placebo (intermittent); 3) placebo, from Monday to Friday. Field workers gave the girls supplements during school hours for 17 wk; 296 girls completed the trial. Girls took 94% of the expected dose of 85 pills. Few side effects were reported. Postintervention, hemoglobin (Hb), serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) were improved significantly in the iron-supplemented groups compared with placebo (P<0.05). Daily supplements led to higher Hb increases than intermittent supplements (P<0.05), but SF and FEP were similar between the two groups. Thus, both iron supplementation schedules were efficacious in preventing iron deficiency in adolescent girls through the school system, and the daily schedule was better than the intermittent schedule at increasing Hb values and reducing anemia.", "In the context of limited effectiveness of iron supplementation programs, intermittent iron supplementation is currently under debate as a possible alternative strategy that may enhance the effectiveness of operational programs. This field-based trial assessed the outcome of twice weekly iron supplementation compared to daily in Pakistan. A double-blind, randomized, clinical trial was conducted in Northern Pakistan. Anemic pregnant women (n = 191) were assigned to receive daily (200 mg ferrous sulfate) or twice weekly (2 x 200 mg ferrous sulfate) iron supplementation. Hemoglobin was measured at baseline and at 4-wk intervals for up to 12 wk. Serum ferritin was measured at baseline and 8 or 12 wk. Analysis was by intention to treat. The two groups did not differ in age, parity, sociodemographic characteristics, hemoglobin or serum ferritin concentrations at baseline. Women who received iron daily had a greater rise in hemoglobin compared with women who received iron twice weekly (17.8 +/- 1.8 vs. 3.8 +/- 1.2 g/L, P < 0.001). The serum ferritin concentrations increased by 17.7 +/- 3.9 microgram/L (P < 0.001) in the daily supplemented group and did not change in the twice weekly group. Daily iron supplementation remained superior to twice weekly supplementation after controlling initial hemoglobin Z-scores and duration of treatment. The body mass index (BMI) modified the effect of daily versus twice weekly iron supplementation. For every unit increase in BMI, the difference between the two treatment groups was reduced by 0.0014 (final hemoglobin Z-score; P = 0.027). We recommend continuation of daily iron supplementation as opposed to intermittent iron supplementation in pregnant women in developing countries.", "It has been suggested that in pregnant women weekly iron supplements are as effective as daily supplements in preventing iron deficiency anaemia (IDA).\n To compare the effectiveness of prophylactic antenatal oral iron supplements given weekly, thrice weekly and daily in preventing IDA in pregnancy.\n A randomised control trial.\n University antenatal clinic, (UANC) Galle.\n An oral iron supplement containing 100 mg of elemental iron was randomly given weekly (n = 26) thrice weekly (n = 35) and daily (n = 31) to 92 women who were 14 to 24 weeks pregnant. Haemoglobin (Hb), serum ferritin (SF) and haematocrit (Hct) were assessed before and after 12 to 20 weeks of supplementation and a logistic regression analysis carried out.\n The risk of developing anaemia was significantly higher in the weekly (odds ratio 15, 95% CI 1.4-165.6, p < 0.03) and possibly higher in the thrice weekly (odds ratio 3, 95% CI 0.3-30.3, p = 0.3) groups. The risk of developing iron deficiency (SF < 12 micrograms/l) was also significantly higher in the weekly (odds ratio 18, 95% CI 2.8-115.5, p < 0.003) and thrice weekly (odds ratio 10, 95% CI 1.6-64.8, p < 0.02) groups.\n Prophylactic oral iron supplements when given intermittently were not effective in preventing iron deficiency anaemia in pregnancy.", "Iron supplementation is recommended for children at high risk of anaemia, but its benefits may not outweigh the associated risk of malaria in areas of seasonal transmission. We investigated the effect on haemoglobin concentrations of intermittent administration of iron supplements and sulfadoxine-pyrimethamine in symptom-free children under intense health surveillance.\n In a trial of two by two factorial design, 328 anaemic Kenyan children were randomly assigned either iron or placebo and sulfadoxine-pyrimethamine or placebo (82 to each group). Primary outcomes were haemological indicators of iron status and inflammation at the end of the follow-up, and occurrence of malaria attacks. Morbidity surveillance consisted of medical examinations every 4 weeks, continuous passive case detection, and visits twice a week to community health-workers. Analyses were by intention to treat.\n After 12 weeks, the groups assigned iron plus sulfadoxine-pyrimethamine, iron alone, or sulfadoxine-pyrimethamine alone had higher haemoglobin concentrations than the group assigned placebo (treatment effect adjusted for prognostic factors at baseline: 11.1 g/L [95% CI 7.5 to 14.7]; 10.7 g/L [7.1 to 14.3]; and 3.1 g/L [-0.5 to 6.7]). Administration of iron plus sulfadoxine-pyrimethamine also lowered the proportion with anaemia from 100% at baseline to 36% at 12 weeks, and of iron deficiency from 66% at baseline to 8% at 12 weeks. Survival analysis showed no evidence of substantially increased risk of malaria after iron supplementation.\n Iron supplementation gives substantial health benefits, which may outweigh possible inherent risks caused by malaria. A larger study than ours is needed to assess benefits and risks of intermittent administration of sulfadoxine-pyrimethamine in reducing the incidence of malaria attacks in areas of seasonal malaria transmission.", "Iron deficiency anemia is a major public health problem in developing countries and may affect school performance and physical work capacity in nonpregnant adolescents, and may increase the risk of anemia during subsequent teenage pregnancies. We assessed the effect of weekly iron (120 mg elemental iron) and vitamin A (25 000 IU) supplementation on hemoglobin, iron status and malaria and nonmalaria morbidity in adolescent schoolgirls.\n A total of 279 schoolgirls aged 12-18 years from public primary schools in Kisumu, western Kenya. Double-blind randomized placebo-controlled trial using a factorial design.\n Five months of iron supplementation was associated with a 0.52 g dl(-1) (0.21, 0.82) greater increase in hemoglobin relative to iron placebo. The effect was only observed in girls with iron deficiency on enrollment (1.34 g dl(-1) (0.79, 1.88)), but not in iron-replete girls (-0.20 g dl(-1) (-0.59, 0.18)). Similar differences in treatment effect were seen between menstruating and nonmenstruating girls. The effect of iron was independent of vitamin A. The baseline prevalence of vitamin A deficiency was low (6.7%) and no sustained increase in hemoglobin was seen with weekly vitamin A (-0.07 g dl(-1) (-0.38, 0.25)). Incidence of malaria parasitemia was higher in the iron than iron-placebo groups (Rate ratio 1.33 (0.94, 1.88)).\n Weekly iron supplementation results in substantial increases in hemoglobin concentration in adolescent schoolgirls in western Kenya, which may outweigh possible risks caused by malaria, but only in iron-deficient or menstruating girls and not in iron-replete and nonmenstruating girls.", "To compare the effectiveness of weekly vs daily iron and folic acid supplementation for control of anemia in adolescent Nepalese girls.\n Randomized controlled trial.\n A Government Girl School in Dharan, Nepal, an urban foothill town that is 305 m above sea level.\n Consecutive healthy adolescent girls (n = 209, median age 15 years) randomized to 3 groups matched for age, anthropometry, and personal and sociodemographic characteristics. Of 209 subjects, 181 completed the trial. Two girls had adverse reactions to treatment and were excluded.\n Group A (n = 70) received a 350-mg ferrous sulfate and 1.5-mg folic acid combination once daily for 90 to 100 days. Group B (n = 67) received the tablet under supervision once a week for 14 weeks. Group C (n = 72) did not receive any drugs.\n Presupplementation and postsupplementation differences in prevalence of anemia and change in hematocrit.\n Prevalence of anemia (defined as hematocrit <36%) declined from 68.6% and 70.1% in groups A and B to 20% and 13.4%, respectively, postsupplementation (P<.001), whereas the prevalence in group C changed little (68.1% to 65.3%, P =.81). There was a significant rise in the mean hematocrit of both supplemented groups (group A, 32.9% +/- 3.5% to 41.0% +/- 5.6%, P<.001; group B, 33.2% +/- 3.6% to 40.4% +/- 4.9%, P<.001) but no appreciable change in controls (34.2% +/- 2.9% to 34.1% +/- 3.3%, P =.91). Net change in mean hematocrit in both the supplementation groups was comparable (P =.57).\n The prevalence of anemia in adolescent Nepalese girls is high. Supervised iron and folic acid therapy once a week is an effective alternative to daily administration and helps lower the prevalence of anemia in adolescent girls.", "Oral iron supplementation is often routinely given to children with malaria-associated anaemia, but its contribution to recovery is controversial. A randomized clinical trial, evaluating such routine, was carried out among 100 children, who had a haemoglobin of < or = 5 g/dl and a positive blood smear for malaria parasites. All children received malaria therapy (chloroquin + fansidar) and were randomly allocated to two groups, one receiving additional oral iron treatment, the other being the control. In the 12-week follow-up period the haemoglobin level and malaria indices were measured at 2, 4, 8, and 12 weeks. There was a 100 per cent compliance during the follow-up period. In each group 20 children (40 per cent) required a blood transfusion. In the remaining 60 children, after 2 weeks the haemoglobin had risen 3.7 g/dl in the ferrous-supplemented group compared to 3.5 g/dl in the non-ferrous group. Thereafter, the increase in haemoglobin in both groups was steady. At follow-up measurements, the groups did not differ for haemoglobin levels. The mean haemoglobin at 12 weeks was 9.2 and 9.0 g/dl, respectively. It was concluded that iron supplementation did not have any effect on the rate of parasitaemia and on parasite density during the 12 weeks. However, the iron-supplemented group had a significantly increased morbidity from other causes than malaria. It appears that iron does not have an effect on the recovery of haemoglobin level in children with malaria-associated anaemia. This study provides no evidence supporting routine iron supplementation to these children." ]

[ "15034503", "21700360", "17451383", "3549810", "1935254", "8129407", "3549809", "8225725", "1428436" ]

[ "A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss.", "A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women.", "Comparison of the efficacy and safety of topical minoxidil and topical alfatradiol in the treatment of androgenetic alopecia in women.", "Topical minoxidil (3%) in extensive alopecia areata, including long-term efficacy.", "Topical minoxidil in the treatment of androgenetic alopecia in women.", "Androgenetic alopecia in the female. Treatment with 2% topical minoxidil solution.", "Double-blind, placebo-controlled evaluation of topical minoxidil in extensive alopecia areata.", "Use of topical minoxidil therapy for androgenetic alopecia in women.", "Treatment of female androgenetic alopecia with minoxidil 2%." ]

[ "To pical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in men with androgenetic alopecia and women with female pattern hair loss. Results can be variable, and historic experience suggests that higher concentrations of topical minoxidil may enhance efficacy.\n The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare the efficacy and safety of 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of female pattern hair loss.\n A total of 381 women (18-49 years old) with female pattern hair loss applied 5% topical minoxidil solution (n = 153), 2% topical minoxidil solution (n = 154), or placebo (vehicle for 5% solution; n = 74) twice daily. Primary efficacy variables were change in nonvellus hair count at week 48, and patient and investigator assessments of change in hair growth/scalp coverage at week 48.\n After 48 weeks of therapy, 5% topical minoxidil was superior to placebo for each of the 3 primary efficacy measures. The 2% topical minoxidil group demonstrated superiority over placebo for hair count and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. The 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit at week 48. Both 5% and 2% topical minoxidil helped improve psychosocial perceptions of hair loss in women with female pattern hair loss. An increased occurrence of pruritus, local irritation, and hypertrichosis was observed with 5% topical minoxidil versus 2% topical minoxidil and placebo.\n In this 48-week study of 381 women with female pattern hair loss, 5% topical minoxidil was superior to placebo on each of the 3 primary efficacy end points: promoting hair growth as measured by change in nonvellus hair count and patient/investigator assessments of hair growth and scalp coverage. Application of 2% topical minoxidil was superior to placebo for assessments of nonvellus hair counts and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. At week 48, the 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit. Both concentrations of topical minoxidil were well tolerated by the women in this trial without evidence of systemic adverse effects. With the introduction of numerous herbal remedies for hair loss, of which most have not been tested in randomized, double-blind, placebo-controlled trials, it is important to describe well-controlled trials that demonstrate the efficacy and safety of topical drugs.", "Although twice-daily application of propylene glycol-containing 2% minoxidil topical solution (MTS) stimulates new hair growth, higher concentrations of minoxidil in a once-daily, propylene glycol-free formulation may improve efficacy and reduce unpleasant side effects.\n We sought to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia.\n A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The primary efficacy parameter was change from baseline in nonvellus target area hair count at week 24. Secondary end points included change in nonvellus target area hair width, overall efficacy by global photographic review as assessed by treatment-blinded evaluators and the subject herself, adverse events, and participants' assessment of product aesthetics.\n After 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with \"the treatment does not interfere with styling my hair\" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS.\n Because of differences in the formulations tested, study participants were not blinded to treatment.\n Once-daily 5% MTF is noninferior and as effective for stimulating hair growth as twice-daily 2% MTS in women with androgenetic alopecia and is associated with several aesthetic and practical advantages.\n Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.", "Two drugs which are approved for the treatment of androgenetic alopecia in women in Germany were compared with regard to their influence on hair growth.\n Patients were randomized to group I (n = 52) who used 2% minoxidil solution twice daily for a period of 12 months or to group II (n = 51) who used 0.025% alfatradiol solution once daily for 6 months and were then switched to 2% minoxidil solution for months 7-12. Changes in hair growth parameters were determined using the TrichoScan.\n Topical treatment with 2% minoxidil solution for 6 months resulted in a significant increase of cumulative hair thickness (p < 0.0001) and absolute hair density (p < or = 0.0025), whereas these parameters of hair growth remained nearly unchanged after 6 months of treatment with alfatradiol solution. Evaluation of the same parameters from month 7 to month 12 demonstrated that 12 months minoxidil treatment resulted in an increasing stabilization (group I). After the alfatradiol-->minoxidil switch in group II a significant increase in cumulative hair thickness (p < 0.0001) and absolute hair density (p < 0.0001) was achieved. Both study medications were well tolerated.\n Treatment with minoxidil can induce an increase in hair density and hair thickness,whereas treatment with alfatradiol results in deceleration or stabilization of hair loss.", "This study was conducted to further evaluate the safety and efficacy of 3% topical minoxidil in the treatment of extensive alopecia areata. Patients were assigned to one of two treatment regimens in a double-blind manner. One group applied 3% minoxidil to the scalp twice daily for 64 weeks; the other group applied placebo for the initial 12 weeks and then switched to 3% minoxidil for the remaining 52 weeks. Thirty male and female subjects, ages 7 to 63 years, with extensive alopecia areata affecting 25% to 100% of the scalp were enrolled, fifteen subjects to each treatment group. Twenty-four of the thirty subjects had greater than 75% scalp hair loss. At 12 weeks the group treated with 3% minoxidil had slightly more hair growth than the placebo group, but the difference was not statistically significant. At 64 weeks, thirteen of twenty subjects (65%) who began with less than full scalp involvement (25% to 99% scalp hair loss) had terminal hair growth that was incomplete or cosmetically acceptable; of these, nine (45%) were cosmetically acceptable, a response that is significant in patients with severe alopecia areata. No hair growth or only slight growth was seen in all nine patients with 100% scalp hair loss at baseline. Thus the extent of hair loss at baseline was correlated with response at 64 weeks. Twenty-one of the patients continued treatment for a second year. Of these, thirteen showed further growth, three had no further growth, and five who had cosmetically acceptable hair growth during the first year had some hair loss.(ABSTRACT TRUNCATED AT 250 WORDS)", "Twenty-eight women with mild to moderate androgenetic alopecia were randomly assigned to apply either 2 percent topical minoxidil or placebo (vehicle) to their involved scalp areas twice daily. At the end of thirty-two weeks, there was a statistically significant increase of nonvellus target area hairs in the minoxidil-treated versus the vehicle-treated group (p = 0.006). Investigator assessment of moderate regrowth showed better results in subjects who used 2 percent topical minoxidil solution than those who used vehicle (p = 0.007), although subjects discerned no difference between treatment groups. Two percent topical minoxidil appears to be effective in the treatment of female androgenetic alopecia.", "Women generally regard their hair loss as socially unacceptable and go to great measures to conceal their problem. In some cases, the negative self-image brought about by hair loss may be the basis of psychiatric illness. The purpose of this study was to evaluate a 2% topical minoxidil solution (Rogaine/Regaine, The Upjohn Co, Kalamazoo, Mich) for the treatment of female androgenetic alopecia. A 32-week, double-blind, placebo-controlled trial was conducted in 11 US centers. Three hundred eight women with androgenetic alopecia were enrolled. Two hundred fifty-six of these women completed the trial. A refined photographic technique was used to objectively determine the number of nonvellus hairs regrown.\n After 32 weeks of treatment, the number of nonvellus hairs in a 1-cm2 evaluation site was increased by an average of 23 hairs in the 2% minoxidil group and by an average of 11 hairs in the placebo group. The 95% confidence interval for the difference in mean hair count change between the treatment groups was 5.9 to 17.5 hairs. The investigators determined that 13% in the minoxidil-treated group had moderate growth and 50% had minimal growth. This compared with 6% and 33%, respectively, in the placebo-treated group. Similarly, 60% of the patients in the 2% minoxidil group reported that they had new hair growth (20% moderate, 40% minimal) compared with 40% (7% moderate, 33% minimal) of the patients in the placebo group. No evaluations of dense hair growth were reported for either treatment group. No clinically significant changes in vital signs were observed and no serious or unexpected medical events were reported.\n Topical minoxidil was significantly more effective than placebo in the treatment of female androgenetic alopecia.", "The safety and efficacy of 3% topical minoxidil were evaluated in the treatment of extensive patchy alopecia areata, alopecia totalis, and alopecia universalis. Patients with extensive patchy alopecia areata had greater than 50% scalp hair loss. In this double-blind study, thirty subjects applied minoxidil or placebo to half of the afflicted scalp area twice daily, with overnight petrolatum occlusion, for 1 year. Both male and female subjects, ranging in age from 9 to 65 years, were enrolled, fifteen subjects to each treatment group. Minoxidil applications were generally well tolerated except for three instances of scalp itching and dermatitis, two of which necessitated discontinuing the medication. Hair growth was seen in seven of eleven evaluable subjects (63.6%) in the minoxidil group and in five of fourteen evaluable subjects (35.7%) in the placebo group. Excellent, cosmetically acceptable hair growth was seen in three of eleven minoxidil-treated subjects (27.3%) and in one of fourteen placebo-treated subjects (7.1%). Examination of vital signs and laboratory measurements revealed no evidence of systemic effects of minoxidil. Seven of the twelve subjects assayed in the minoxidil group had detectable minoxidil serum levels, ranging from 0.4 to 7.5 ng/ml.", "Androgenetic alopecia is the most common cause of hair loss in men and women. Androgenetic alopecia in women begins as a diffuse and progressive thinning of the frontoparietal area of the scalp. In women, hair loss at any age is socially unacceptable and may be the basis of psychiatric illness.\n A 32-week, double-blind, placebo-controlled trial was conducted in 10 European centers to assess the efficacy and safety of 2% topical minoxidil solution for the treatment of androgenetic alopecia in women. Two hundred ninety-four of the 346 women enrolled (85%) completed the 32-week trial. Photographic and computer imaging techniques were used at each visit to determine objectively the number of nonvellus hairs present in a 1-cm2 area selected as the target evaluation site.\n In the 2% minoxidil group, the mean increase in nonvellus hair count was 33 hairs, which was significantly greater than that of 19 hairs in the placebo group (P = 0.0001). The investigators observed that 44% of the patients in the 2% minoxidil group achieved new hair growth compared with 29% in the placebo group. When asked to evaluate their own hair growth, 55% of the women in the 2% minoxidil group compared to 41% of the women in the placebo group believed that they had achieved new hair growth. No clinically significant changes in vital signs were observed during the study and no serious or unexpected medical events were reported.\n Topical minoxidil solution was significantly more effective than placebo in the treatment of androgenetic alopecia in women.", "The safety and efficacy of minoxidil 2% for the treatment of female androgenetic alopecia was assessed in a 32-week double-blind placebo-controlled trial. Thirty-three women aged 22 to 44 years with hair loss classified as Ludwig's grade I or II were enrolled, and 28 completed the trial. Before the administration of treatment, mean nonvellus hair counts were taken within a 1-cm2 target area of the scalp. For the 15 patients in the minoxidil group, the mean count was 169 hairs compared with 161 hairs for the 13 patients in the placebo group. At the completion of the trial, the patients treated with minoxidil 2% had a mean nonvellus hair count of 195 hairs versus a mean hair count of 177 for patients in the placebo group; 60% (9) of the patients in the minoxidil group showed minimal to moderate hair growth compared with 46% (6) of the patients in the placebo group. No serious side effects were encountered during this study, nor any significant changes in safety parameters. There were no dropouts due to medical events related to minoxidil 2%." ]

[ "12009350", "16818032", "16984757", "9804219", "11006179", "9457941", "7989521", "12042269", "19568761" ]

[ "Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist.", "Delaying the initiation of progesterone supplementation until the day of fertilization does not compromise cycle outcome in patients receiving donated oocytes: a randomized study.", "Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer.", "Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study.", "Prospective randomized trial to evaluate the efficacy of a vaginal ring releasing progesterone for IVF and oocyte donation.", "Experience with a novel vaginal progesterone preparation in a donor oocyte program.", "Human menopausal gonadotrophin increases pregnancy rate in comparison with clomiphene citrate during replacement cycles of frozen/thawed pronucleate ova.", "A prospective randomized study: day 2 versus day 5 embryo transfer.", "Local injury to the endometrium on the day of oocyte retrieval has a negative impact on implantation in assisted reproductive cycles: a randomized controlled trial." ]

[ "To test the efficacy of endometrial preparation with exogenous steroids, without pretreatment with gonadotropin-releasing hormone (GnRH) agonist, in women with normal ovarian function.\n Prospective randomized study.\n Private outpatient infertility clinic.\n Two hundred ninety-six women undergoing frozen-thawed embryo transfer.\n In group 1 (146 patients), depot GnRH agonist was administered in the luteal phase; treatment with 17beta-estradiol transdermal patches at steadily increasing dosage from 100 to 300 microg was then given for at least 12 days. In group 2 (150 patients), endometrial preparation began on day 1 of menstrual cycle. The starting dose was 200 microg; this was increased to 300 microg after 7 days.\n Pregnancy, abortion, implantation and cancellation rates.\n In group 2, six cycles (4%) were cancelled due to evidence of ovulation. Groups were similar in the percentage of embryos that survived freezing-thawing (77.1% in group 1 and 76.6% in group 2) and in the number of embryos transferred per patient (2.1 +/- 0.6 and 2.1 +/- 0.7, respectively). Groups 1 and 2 did not differ significantly in rates of pregnancy (19.7% and 24.1%), abortion (17.8% and 11.7%), and implantation (10.4% and 11.9%).\n Endometrial preparation for frozen-thawed embryo transfer based exclusively on steroid administration appears to be as effective as the more conventional protocol involving preliminary desensitization with a GnRH agonist. This simplified protocol reduces costs, minimizes pharmacologic treatment, and increases patient compliance.", "To determine whether the initiation of P supplementation as artificial luteal phase support (day -1, day 0, or day +1 of egg donation) in extensive programs of ovum donation influences cycle cancellation, pregnancy outcome, and implantation rate in day 3 embryo transfers.\n Prospective randomized trial.\n Oocyte donation program at the Instituto Valenciano de Infertilidad, Valencia, Spain.\n Three hundred recipients with normal ovarian function, absence of uterine anomalies, and undergoing their first egg donation were recruited between September 2003 and September 2004.\n A computer-based randomization divided the recipients into three groups when hCG was administered to their matched donors. The first group (group A) started P supplementation the day before oocyte retrieval; the second group (group B) started P supplementation on the day of the oocyte retrieval; and the third group (group C) started P supplementation 1 day after the egg retrieval once fertilization was confirmed.\n Implantation, pregnancy, and ongoing pregnancy rates were the primary outcome measures considered. The secondary outcome measure was the cancellation rate, especially due to fertilization failure.\n Global cancellation rate and cancellation rate due to fertilization failure were significantly higher in group A (12.4% and 8.2%, respectively) than in group C (3.3% and 0%, respectively). Reproductive outcome was similar in all the groups except for a higher biochemical pregnancy rate in group A (12.9%) than in groups B (6.6%) and C (2.3%).\n Initiation of P on day +1 of embryo development decreases cancellation rates of day 3 embryo transfers in extensive programs of ovum donation without any deleterious effect on pregnancy outcome or implantation rate.", "The objective of this study was to compare the implantation rate, pregnancy rate and endometrial thickness of frozen-thawed embryo transfers using endometrial preparation with either an artificial cycle or stimulated cycle. This was a prospective randomized trial at a single academic IVF centre. Seventy-seven patients undergoing artificial cycles received oral oestradiol; patients with endometrium < 7 mm on day 9-10 were switched to vaginal oestradiol. Eighty-six patients undergoing stimulated cycles received recombinant FSH followed by human gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior to embryo transfer. There was no difference in implantation rate (8.5% versus 7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or endometrium thickness (8.7 +/- 1.1 mm versus 8.7 +/- 1.0 mm) between artificial and stimulated cycles. Stimulated cycles had a higher incidence of thin endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to vaginal oestradiol had improved pregnancy rate (31%) versus patients who received oral oestradiol alone (13%) (P = 0.05). It is concluded that artificial and stimulated cycles produce comparable pregnancy rates, implantation rates, cancellation rates and endometrial thickness, although stimulated cycles have a higher incidence of thin endometrium. Vaginal oestradiol supplementation improved implantation rates.", "Transfer of frozen-thawed embryos is usually carried out in a natural cycle or in a programmed cycle in which the endometrium is exogenously stimulated following down-regulation of the hypophysis. To analyse the possibility that the programmed cycle for embryo transfer can still be hormonally manipulated without the use of gonadotrophin-releasing hormone agonist (GnRHa) we have conducted a prospective randomized study that compared the outcome of frozen-thawed embryo transfer cycles using micronized 17beta-oestradiol and micronized progesterone preparations with and without the concomitant use of GnRHa. One hundred and six patients were randomly divided into two groups. In group A (53 patients) 4 mg/day of micronized 17beta-oestradiol was initiated following down-regulation of hypophysis. In group B (53 patients) oestrogen stimulation started on day 1 of the cycle without prior pituitary down-regulation using a dose of 6 mg/day for 7 days. In both groups, micronized progesterone in a dose of 900 mg/day was administered vaginally after at least 12 days of oestrogen stimulation. Embryo transfer embryo transfer took place 48-72 h thereafter according to the cryopreserved embryonic stage. Overall, none of the patients had any follicular development and only one cycle in group B had to be cancelled because of premature progesterone secretion. The two groups did not differ in age (31+/-5.6 and 31+/-5.0 years), number of embryos transferred per patient (3.4+/-1.2 and 3.3+/-1.0), and day of progesterone initiation (15+/-2.2 and 15+/-1.9 for groups A and B respectively). The endometrial thickness on the day of progesterone initiation was comparable in both groups (11 +/-1.6 and 10+/-1.6 mm for groups A and B respectively). Similarly, the pregnancy rate per embryo transfer and implantation rate in group A (26.4% and 9.5%) were comparable to those of group B (21.1% and 9%). These results indicate that programmed cycles can be successfully applied by administering a high dose of micronized 17beta-oestradiol starting on day 1 of the cycle. Compared to GnRHa programmed cycles, this approach is simpler, more convenient for both the patient and medical staff, and results in a similar success rate at a lower cost.", "A polysyloxane vaginal ring containing 1g of natural progesterone was developed as luteal supplementation for women treated with IVF-embryo transfer and for agonadal women participating in an oocyte donation programme. The ring provides continuous release of progesterone (10-20 nmol/l) for 90 days. The efficacy of this form of progesterone supplementation was evaluated in two multicentre prospective randomized trials. IVF-embryo transfer trial: After oocyte aspiration, 505 women were randomly allocated to progesterone supplementation with vaginal ring or i.m. progesterone (50 mg/day). The clinical pregnancy rate was 36.6% in both groups. Implantation rate was 15.9% in the vaginal ring and 16.0% in i.m. progesterone. Oocyte donation trial: After endometrial proliferation with micronized oestradiol, 153 women were allocated to progesterone replacement with a vaginal ring or i.m. progesterone (100 mg/day). Clinical pregnancy rate was 39.8 and 28.6% respectively. Implantation rate was significantly higher with the vaginal ring compared with i.m. progesterone (19.9 and 11.6% respectively, P = 0.006). The vaginal ring is a novel development which provides continuous release of progesterone for 90 days. In IVF-embryo transfer, its effectiveness is similar to daily i.m. injections. In oocyte donation the ring provides a progestative milieu which improves the implantation rate and eliminates the discomfort of daily i.m. injections.", "To compare the efficacy of a vaginal progesterone preparation with our standard IM preparation within a donor egg program.\n Prospective randomized trial.\n Donor egg program at a university assisted reproductive therapy program (Jones Institute for Women's Health).\n Couples accepted into the donor egg program because of either premature ovarian failure or evidence of diminished ovarian reserve.\n Women were randomized into either a group receiving IM progesterone replacement or a group receiving vaginal progesterone replacement. Both groups underwent Estraderm patch/progesterone treatment in a mock cycle leading to an endometrial biopsy on day 26 followed by a second cycle in which ET was performed. Subjects with residual ovarian function received a GnRH agonist. In the IM treatment group, 100 mg was administered from cycle days 15 to 27. In the vaginal treatment group, Crinone 8%, a polycarbophil-based gel preparation containing 90 mg of micronized progesterone, was administered twice daily from the evening of day 14.\n Endometrial histology, serum levels of progesterone (on days 13, 17, 20, 24, and 26), the occurrence of pregnancy, implantation rate, and pregnancy outcome.\n Fifty-four women randomized into the vaginal progesterone treatment group and 18 women in the IM treatment group achieved ET. Mean serum progesterone levels were higher in the IM treatment group than in the Crinone group. Endometrial histology was \"in phase\" for all subjects in both groups. Clinical pregnancies were observed in 26 of 54 women and 5 of 18 women in the Crinone and IM progesterone groups, respectively. The ongoing pregnancy rate (PR) of 31% (17/54) and implantation rate of 23% in the subjects receiving Crinone was not statistically different from the IM progesterone group's ongoing PR of 22% (4/18) and implantation rate of 18%.\n Vaginal progesterone replacement with the polycarbophil gel preparation was as effective as IM progesterone in producing clinical and ongoing pregnancies within our donor egg program in the dosages administered.", "In a prospective randomized study, the effect of two ovulation induction regimens on implantation rate of frozen/thawed pronucleate ova was investigated. Patients received either human menopausal gonadotrophin (HMG) or clomiphene/HMG. Ovulation induction was done on an individual basis using ultrasound and plasma 17 beta-oestradiol concentrations. Ovulation was induced with human chorionic gonadotrophin (HCG) when the leading follicle reached a diameter of 18 mm. Pronucleate ova had been frozen using the slow-freezing method of Lassalle et al. (1985) (Fertil. Steril., 44, 645-651) and were thawed in synchrony with the age of the endometrium. Both groups of patients were comparable for age, indication for in-vitro fertilization, pre-ovulatory 17 beta-oestradiol concentration, number of large follicles and number and quality of embryos transferred. The only difference found was that HCG was administered 1 day earlier in the HMG group compared to the clomiphene/HMG group (P < 0.01). Using univariate analysis, the pregnancy rate was higher in patients stimulated with HMG alone compared to those stimulated with clomiphene/HMG (27 versus 15% respectively; P < 0.03), when HCG was administered later in the menstrual cycle (P < 0.01) and when more and better quality embryos were transferred (P < 0.01). Using multivariate regression analysis, the influence of the stimulation on pregnancy rate was even more pronounced (P < 0.01) when the day of HCG administration and the number and quality embryos transferred were taken into account. Therefore, we conclude that HMG alone increases pregnancy rate compared to clomiphene/HMG during replacement cycles of frozen/thawed pronucleate ova. These data suggest that HMG results in a better endometrium receptivity for embryos.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "To evaluate the effect of local injury to the endometrium on the day of oocyte retrieval on implantation and pregnancy rates in assisted reproductive cycles.\n In a prospective controlled trial, a total of 156 patients, <38 years old, in their first in vitro fertilization (IVF) cycle were randomized. In 77 patients, two small endometrial samples from anterior and posterior walls of uterus were obtained with a Novak curette on the day of oocyte retrieval and in 79 patients no intervention was performed.\n The experimental and control patients were matched regarding women's age, body mass index, basal FSH, duration and etiology of infertility, treatment protocol, number of retrieved oocyte, endometrial thickness, percentage of intracytoplasmic sperm injection performance, fertilization rate, the percentage of patients with good and top quality embryos, and the number of embryos transferred. The implantation rate (7.9 vs. 22.9%), clinical (12.3 vs. 32.9%; odds ratio = 0.25; 95% confidence interval = 0.12-0.66; p < 0.05) and ongoing pregnancy (9.6 vs. 29.1%; odds ratio = 0.25; 95% confidence interval = 0.10-0.64; p < 0.05) rates were significantly lower in experimental group, compared with 79 controls.\n According to the results of this study, local injury to the endometrium on the day of oocyte retrieval disrupts the receptive endometrium and has a negative impact on implantation and IVF outcomes." ]

[ "20216531", "15944167", "16819378", "8201068", "19695776", "10896070", "21681863", "16979581", "9300508" ]

[ "Cognitive-behavioral therapy for children with functional abdominal pain and their parents decreases pain and other symptoms.", "A randomized controlled trial of a cognitive-behavioral family intervention for pediatric recurrent abdominal pain.", "Treatment of nonorganic recurrent abdominal pain: cognitive-behavioral family intervention.", "The treatment of recurrent abdominal pain in children: a controlled comparison of cognitive-behavioral family intervention and standard pediatric care.", "Randomized controlled trial of an Internet-delivered family cognitive-behavioral therapy intervention for children and adolescents with chronic pain.", "Treatment of recurrent abdominal pain: components analysis of four treatment protocols.", "Cognitive-behavioral treatment of persistent functional somatic complaints and pediatric anxiety: an initial controlled trial.", "A controlled evaluation of group cognitive therapy in the treatment of irritable bowel syndrome.", "A controlled trial of cognitive behavioural therapy for non-cardiac chest pain." ]

[ "Unexplained abdominal pain in children has been shown to be related to parental responses to symptoms. This randomized controlled trial tested the efficacy of an intervention designed to improve outcomes in idiopathic childhood abdominal pain by altering parental responses to pain and children's ways of coping and thinking about their symptoms.\n Two hundred children with persistent functional abdominal pain and their parents were randomly assigned to one of two conditions-a three-session intervention of cognitive-behavioral treatment targeting parents' responses to their children's pain complaints and children's coping responses, or a three-session educational intervention that controlled for time and attention. Parents and children were assessed at pretreatment, and 1 week, 3 months, and 6 months post-treatment. Outcome measures were child and parent reports of child pain levels, function, and adjustment. Process measures included parental protective responses to children's symptom reports and child coping methods.\n Children in the cognitive-behavioral condition showed greater baseline to follow-up decreases in pain and gastrointestinal symptom severity (as reported by parents) than children in the comparison condition (time x treatment interaction, P<0.01). Also, parents in the cognitive-behavioral condition reported greater decreases in solicitous responses to their child's symptoms compared with parents in the comparison condition (time x treatment interaction, P<0.0001).\n An intervention aimed at reducing protective parental responses and increasing child coping skills is effective in reducing children's pain and symptom levels compared with an educational control condition.", "To investigate whether the combination of standard medical care (SMC) and short-term cognitive-behavioral family treatment (CBT) in the treatment of recurrent abdominal pain (RAP) was more effective than SMC alone.\n Children recently diagnosed with RAP via physician examination were randomized into SMC (n = 29) and SMC plus CBT (n = 40) groups. Outcome measures included multiple dimensions of child and parent reported child pain, somatization, and functional disability, and school absences and physician contacts.\n Children and parents participating in the combined SMC + CBT intervention reported significantly less child and parent reported child abdominal pain than children in the SMC intervention immediately following the intervention and up to 1 year following study entry, as well as significantly fewer school absences. Significant differences in functional disability and somatization were not revealed.\n These results, in combination with previous studies, add support to the effectiveness of CBT intervention in reducing the sensory aspects of RAP. Results are discussed with respect to the cost-benefit of integrated medical and short-term psychological services.", "We evaluated the efficacy of cognitive-behavioral family intervention in the treatment of crises of pain in children with nonorganic recurrent abdominal pain (RAP) and the thresholds of pain for 17 body surface areas in these children.\n A randomized clinical trial was undertaken with 32 children between the ages of 5.1 and 13.9 years with nonorganic RAP. A group of 15 patients, aged 9.9 +/- 2.2 years (11 girls), received standard pediatric care and cognitive-behavioral family intervention for treatment of pain crises. The control group of 17 children, aged 8.4 +/- 2.0 years (11 girls), received only standard pediatric care. These procedures were undertaken by general pediatricians over 4 monthly sessions. An analog visual scale was used to measure the frequency and intensity of the pain crises per month and a mechanical pressure algometer for the measurement of pain threshold.\n The median frequency of pain crises per month reported by patients at the 3 monthly cognitive-behavioral family intervention sessions was 15, 5, 2 and 2, respectively. In contrast, the median frequency for pain crises per month reported by the control group was 12, 8, 10 and 8, respectively. The difference between the intervention group and the controls was statistically significant for frequency of pain at the second, third and fourth visits. There was no statistical difference for intensity of pain or for measured pain thresholds between the control and the intervention group.\n The cognitive-behavioral family intervention reduced the frequency of pain crises of children with nonorganic RAP. This successful intervention was carried out by the intervention of general pediatricians.", "This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment.", "Cognitive-behavioral therapy (CBT) interventions show promise for decreasing chronic pain in youth. However, the availability of CBT is limited by many factors including distance to major treatment centers and expense. This study evaluates a more accessible treatment approach for chronic pediatric pain using an Internet-delivered family CBT intervention. Participants included 48 children, aged 11-17 years, with chronic headache, abdominal, or musculoskeletal pain and associated functional disability, and their parents. Children were randomly assigned to a wait-list control group or an Internet treatment group. Primary treatment outcomes were pain intensity ratings (0-10 NRS) and activity limitations on the Child Activity Limitations Interview, both completed via an online daily diary. In addition to their medical care, the Internet treatment group completed 8 weeks of online modules including relaxation training, cognitive strategies, parent operant techniques, communication strategies, and sleep and activity interventions. Youth randomized to the wait-list control group continued with the current medical care only. Findings demonstrated significantly greater reduction in activity limitations and pain intensity at post-treatment for the Internet treatment group and these effects were maintained at the three-month follow-up. Rate of clinically significant improvement in pain was also greater for the Internet treatment group than for the wait-list control group. There were no significant group differences in parental protectiveness or child depressive symptoms post-treatment. Internet treatment was rated as acceptable by all children and parents. Findings support the efficacy and acceptability of Internet delivery of family CBT for reducing pain and improving function among children and adolescents with chronic pain.", "Recurrent abdominal pain (RAP) affects up to 34% of the world's population of children. Medical management has been limited, but behavioral strategies have been shown to be effective. In this study several components of published treatment protocols were adapted and/or improved and then compared using a pretest-posttest control group design.\n Sixty-four children and teenagers (mean age, 9.75 +/- 2.46 years) with diagnosed recurrent abdominal pain were randomly assigned to four groups: 1) fiber-only comparison group; 2) fiber and biofeedback-assisted cultivated low arousal; 3) fiber, biofeedback, and cognitive-behavioral interventions; and 4) fiber, biofeedback, cognitive-behavioral, and parental support. Participants were treated over 8 weeks in individual sessions. Biofeedback was supplied using small thermal devices.\n All groups showed improvement in self-reported pain, even the fiber-only comparison group; however, the active treatment groups showed significantly more improvement before and after than the fiber-only comparison group (fiber only comparison group pain reduction at 79%; fiber and biofeedback at 100%; fiber, biofeedback, and cognitive-behavioral at 94%; fiber, biofeedback, cognitive-behavioral, and parental support at 93%).\n This suggests that any of the active treatment protocols assessed in this investigation work better than established treatments that have been reported in the literature. Because the addition of cognitive and parental support components did not seem to increase treatment effectiveness, it is concluded that increased fiber with biofeedback-assisted cultivated low arousal was effective and efficient as a treatment modality.", "Children and adolescents who seek medical treatment for persistent physical distress often suffer from co-occurring anxiety disorders. Treatment options for this impaired population are limited. This study tests the feasibility and potential efficacy of a cognitive-behavioral intervention targeting pain and anxiety for youth with impairing functional physical symptoms and anxiety disorders presenting to pediatricians for medical care.\n Children and adolescents (aged 8-16) experiencing somatic complaints, without an explanatory medical disorder (i.e., functional), were recruited from primary care and specialty (gastroenterologists and cardiologists) pediatricians. Forty children, primarily with gastrointestinal symptoms, who met criteria for a co-occurring anxiety disorder, were randomly assigned to a cognitive-behavioral treatment addressing pain and anxiety, Treatment of Anxiety and Physical Symptoms (TAPS), or to a waiting list control.\n TAPS was found to be an acceptable treatment for this population and was superior to the waiting list condition. Eighty percent of children in TAPS were rated as treatment responders by independent evaluators compared with none of the controls. Overall, self- and parent ratings indicated reductions in children's somatic discomfort and anxiety following intervention. TAPS participants maintained clinical gains 3 months following treatment.\n The study supports the feasibility and preliminary efficacy of a cognitive-behavioral intervention targeting co-occurring physical distress and anxiety in youth presenting for medical treatment. Such an approach has the potential to exert broad impact on children's dysfunction and to minimize exposure to invasive, ineffective, and costly medical procedures and treatments.\n © 2011 Wiley-Liss, Inc.", "We randomized, at two sites, 210 patients with Rome II diagnosed irritable bowel syndrome (IBS), of at least moderate severity, to one of three conditions: group-based cognitive therapy (CT; n=120), psychoeducational support groups (n=46) as an active control, or intensive symptom and daily stress monitoring (n=44). One hundred eighty-eight participants completed the initial treatment. Those in symptom monitoring were then crossed over to CT. For an intent to treat analysis on a composite GI symptom measure derived from daily symptom diaries, both CT and the psychoeducational support groups were significantly more improved than those in the intensive symptom monitoring condition, but the CT and psychoeducational support group did not differ. Among treatment completers on the same composite measure of GI symptoms, again, both CT and psychoeducational support groups were statistically superior to symptom monitoring but did not differ on the symptom composite, or on any other measure. On individual IBS symptoms, both CT and psychoeducational support were statistically superior to symptom monitoring on reductions in abdominal pain and tenderness and for flatulence. Patient global ratings at the end of treatment showed the two active conditions statistically superior to symptom monitoring on change in Bowel Regularity, with CT superior to symptom monitoring on reduction in overall pain and in improvement in sense of well-being. Three-month follow-up data on 175 patients revealed maintenance of significant improvement or continued significant improvement on all IBS symptoms, including the McGill Pain Questionnaire. Group CT and psychoeducational support groups continued not to differ on any measure. We thus conclude that group CT is not superior to an attention placebo control condition.", "The majority of patients presenting to cardiac clinics with chest pain who are reassured they do not have heart disease or other serious physical disorder continue to experience symptoms, worry about heart disease and restrict their activities. This randomized trial investigated the effectiveness of psychological treatment within routine cardiac care.\n Consecutive patients presenting with chest pain and reassured by a cardiologist they do not have heart disease were reassessed 6 weeks later. Those with persistent limiting symptoms were offered the opportunity to participate in a trial of cognitive behavioural therapy.\n Thirty-seven subjects agreed to take part. A number of subjects were unenthusiastic about psychological intervention or, following explanation of the study, regarded further treatment as not being necessary. At 3 months there were significant differences between the treatment group and the control group on key outcome measures of symptoms, mood and activity. At 6 months there were fewer differences but significant advantages of treatment in terms of limitation of activities and worry about physical symptoms.\n We conclude that there is a need for 'stepped' further care following reassurance in the cardiac clinic and that cognitive behavioural treatment is effective with those with persistent disabling symptoms." ]

[ "10765510", "791584", "3475231", "2242793", "7052115", "19250367", "3504454", "780062", "6584028" ]

[ "Randomized trial of administration of prostaglandin E2 gel for induction of labor in the morning or the evening.", "Double-blind trial of prostaglandin F2alpha and oxytocin in the induction of labour.", "[Comparison between prostaglandin E2 gel and oxytocin in medically indicated labor induction].", "Induction of labour: the effect of vaginal prostaglandin or i.v. oxytocin--a matter of time only?", "Induction of labour: a comparison of a single prostaglandin E2 vaginal tablet with amniotomy and intravenous oxytocin.", "Start of induction of labour with oxytocin in the morning or in the evening. A randomised controlled trial.", "Cervical ripening and labor outcome with preinduction intracervical prostaglandin E2 (Prepidil) gel.", "A randomised controlled trial of an oral solution of prostaglandin E2 and oral oxytocin used immediately after low amniotomy for induction of labour in the presence of a favourable cervix.", "The effect of vaginal prostaglandin E2 pessaries on induction of labor." ]

[ "To compare the outcome of induction of labor and patient's preferences using a protocol with the first dose of prostaglandin E2 endocervical gel in the evening versus a protocol with the first dose in the morning.\n We performed a randomized trial comparing administration of prostaglandin E2 endocervical gel in the morning with administration of prostaglandin E2 gel in the evening, followed if necessary by a second dose being given after six hours if labor had not started or the cervix was still unripe. Formal induction of labor by amniotomy and oxytocin infusion was performed the morning after the initial prostaglandin E2 dose. Patients' preferences were assessed using a questionnaire that was completed after delivery.\n Tertiary care hospital in the Netherlands with 1,600 deliveries per year.\n One-hundred and twenty-six women with viable singleton pregnancies at term who had induction of labor with prostaglandins.\n Time of delivery (daytime, evening or night) and patient's satisfaction.\n Fifty-eight women were allocated for administration of gel in the morning, whereas 68 had their gel in the evening. Administration of gel in the evening did not significantly reduce delivery between 23.00 hours and 08.00 hours, although there was a reduction in delivery between 23.00 hours and 08.00 hours in nulliparae. None of the multiparous women delivered between 18.00 hours and 23.00 hours after induction of labor in the evening. The relative risk for delivery by vacuum or forceps was increased after allocation of gel in the evening (4.2; 95% confidence limits 1.4 to 13). Patients' preferences favored administration of gel in the morning.\n There was no benefit in starting induction of labor with prostaglandin E2 in the evening, compared with starting in the morning.", "In a random double-blind trial in 28 pregnant women at term, labour was induced with either prostaglandin F2alpha or oxytocin given by intravenous infusion. The results showed that prostaglandin F2alpha was as active as oxytocin and induction was successfully carried out in 24 patients; 3 patients had a caesarean section because of an obstructed labour and 1 patient on oxytocin did not have regular contractions after 10-hours' infusion although she delivered spontaneously 2 days later. No difference was found in the induction--delivery interval in the 8 patients in each group who had early amniotomy (first 90 minutes). No adverse effects were noted in either mother or the child. The authors recommend that to avoid side-effects the dosage of 20 mug prostaglandin F2alpha per minute should not be exceeded and that, although no cardiotocographic abnormalities were noted, this method of control should be used.", "The use of prostaglandins (PG) increasingly replaces the \"classical\" method of induction of labour by means of oxytocin and amniotomy, the last-named method being associated, especially in women with an unripe cervix, with side effects like prolonged labour and a higher rate of obstetric surgery. In this study the point of interest was whether prostaglandins offer any advantages over the classical method in respect of efficacy and maternal and foetal tolerance. 99 patients subdivided into primiparae and multiparae were randomly assigned to group A or B. In group A labour was induced with 1 mg resp. 2 mg PGE2 intravaginally at an interval of 6 hours. In group B the method of induction consisted of intravenous oxytocin and amniotomy. The success rate of induction was almost equal in both groups. However, in those patients where PGE2 induction did not succeed and who could not be delivered within 12 hours the cervical score was significantly improved in comparison to the oxytocin group. Based on the experience reported in the literature, one might speculate that an increased dosage could still improve the results of vaginally administered PGE2 gel.", "Ninety-one pregnant women with unfavourable cervix (Bishop score no higher than 6) were randomly allocated to induction of labour with either prostaglandin E2 suppositories 2.5 mg 1-2 a day or i.v. oxytocin 4-32 mU/min. The induction procedure was carried on for 2 days. For statistical comparison of efficacy, life table analysis and the logrank test were used with vaginal delivery as the aimed 'event'. Prostaglandin suppositories were more efficient after 12 h (p less than 0.025) and 24 h (p less than 0.005), whereas no difference in efficacy was observed after 48 h. Vaginal delivery was obtained within 48 h in 74% of the women in the prostaglandin group and in 70% in the oxytocin group. No difference was observed in methods of delivery or neonatal Apgar scores, though, in neonates delivered vaginally within 2 days, lowered umbilical artery blood pH values were found after prostaglandin E2 suppositories (p less than 0.05). The patients attitude toward the method of induction was highly in favour of the prostaglandin suppositories. Prostaglandin E2 suppositories are considered excellent for induction of labour if delivery has to be within 24 h, whereas the two methods are equally effective after 48 h.", "In a randomized controlled study of 100 women of low parity and favourable induction features, induction of labour by means of a single vaginal tablet containing 3 mg of prostaglandin E2 (PGE2) was compared with the conventional method of amniotomy and intravenous oxytocin. Four of the patients (8%) who received the prostaglandin tablet required additional intravenous oxytocin to achieve delivery. The prostaglandin group had a longer mean overall induction-delivery interval but a shorter amniotomy-delivery interval than the oxytocin group. One patient in the PGE2 group and two in the oxytocin group required caesarean section. The PGE2 treated patients expressed a higher level of satisfaction with their method of induction, they required less analgesia, had less blood loss at delivery and their babies had a lower incidence of neonatal jaundice.", "The objective of this study was to compare outcomes of induced labour with intravenous oxytocin with a start in the evening versus in the morning.\n Randomised controlled trial.\n Labour wards of three hospitals in Amsterdam, the Netherlands.\n Women with an indication for induction of labour with intravenous oxytocin.\n Included women were randomized to either the evening group with a start of induction of labour at 21:00 hours, or the morning group with a start at 07:00 hours.\n Primary outcome was duration of labour. Secondary outcomes were instrumental delivery rate, adverse neonatal outcome defined as an Apgar score below 7 after 5 minutes, number and indications of paediatric consults and neonatal admissions, duration of second stage, number of intrapartum infections and necessity of pain relief.\n We randomised 371 women. Mean duration of labour was not significantly different (primiparae: morning 12 hours and 8 minutes versus evening 11 hours and 22 minutes, P value 0.29; multiparae: morning 7 hours and 34 minutes versus evening 7 hours and 46 minutes, P value 0.70). There were no significant differences in instrumental deliveries rates, number of infections or patient satisfaction. Unexpectedly, neonatal outcome was better in women induced in the evening.\n Induction of labour with intravenous oxytocin in the evening is equally effective as induction in the morning.", "Delivery with an unfavorable cervix using oxytocin is frequently unsuccessful. Used widely in Europe and increasingly in this country, locally applied prostaglandin E2 appears to improve labor induction. The present study prospectively evaluated the efficacy and safety of a prostaglandin gel (0.5 mg) placed intracervically. The use of the gel, when compared to a control group who received no pretreatment prior to labor induction, resulted in improved Bishop scores (7.5 +/- 1.0 vs. 1.8 +/- 0.3, P less than 0.0001), reduced induction to delivery intervals (10.1 +/- 2.1 vs. 20.6 +/- 2.0 hours), reduced oxytocin infusion duration (10.0 +/- 2.1 vs. 20.0 +/- 2.3 hours. P less than 0.0001) resulting in a lower cesarean delivery rate, 26 vs. 47 per cent (P greater than 0.05). Thirty-two per cent of patients receiving the prostaglandin gel labored and delivered within 12 hours and required no oxytocin. In addition, the use of prostaglandin E2 gel appeared safe in that no patient experienced an untoward reaction. Two cases of uterine hyperstimulation occurred that required uterine tocolysis but were not associated with fetal distress. The use of prostaglandin gel appears to be a safe and effective method to improve cervical inducibility in patients undergoing induction for a variety of maternal and fetal indications.", "A randomised controlled trial was carried out in 50 primigravidae and 50 multigravidae to compare the effectiveness in induction of labour after low amniotomy of prostaglandin E2, given as an oral solution, and oxytocin, given as buccal tablets. The results showed that in dosages recommended by the manufacturers, both oxytocic preparations were almost equally effective. With oral oxytocin, once labour had been established and dosage was left to the discretion of the staff, there appeared to be a potentially dangerous tendency to continue giving large doses despite adequate uterine contractions. The authors comment that this was probably the reason why oxytocin-treated multigravidae having normal deliveries within 24 hours had labours significantly shorter on average than those of other successfully induced patients.", "In a prospective randomized study, patients with a valid obstetric indication for induction of labor received either 3 mg prostaglandin E2 vaginal pessaries immediately prior to oxytocin (prostaglandin group, n = 99), or oxytocin alone (oxytocin group, n = 103). At the conclusion of the second day of induction, a significant reduction was noted in the incidence of failed induction in the prostaglandin group (4%) as compared to the oxytocin group (13%) (p less than 0.05). Twenty percent of patients in the prostaglandin group experienced successful induction with prostaglandin pessaries only. When oxytocin was required in the prostaglandin group, the maximal concentration of oxytocin infused and the duration at this concentration were significantly less than in the oxytocin group. No perinatal complications were attributed to the use of prostaglandin. Three minor maternal complications that were attributed to vaginal prostaglandin E2 did not require treatment. Our conclusion is that patients who require an induction of labor, when artificial rupture of the membranes is not feasible, benefit from the use of prostaglandin pessaries before the administration of oxytocin." ]

[ "7726322", "10907738", "10023500", "11254020", "11281989", "9160600", "1102877", "3539028", "2941771" ]

[ "Double-blind, controlled trial of inositol treatment of depression.", "Inositol addition does not improve depression in SSRI treatment failures.", "Combination of inositol and serotonin reuptake inhibitors in the treatment of depression.", "Inositol as an add-on treatment for bipolar depression.", "Inositol versus placebo augmentation of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: a double-blind cross-over study.", "Inositol treatment of post-traumatic stress disorder.", "A controlled trial of maprotiline (Ludiomil) in depressed outpatients.", "Respiratory distress syndrome and inositol supplementation in preterm infants.", "A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression." ]

[ "CSF levels of inositol have been reported to be lower than normal in depressed subjects. The authors administered inositol to depressed patients in a double-blind, controlled trial.\n Under double-blind conditions, 12 g/day of inositol (N = 13) or placebo (N = 15) was administered to depressed patients for 4 weeks.\n The overall improvement in scores on the Hamilton Depression Rating Scale was significantly greater for inositol than for placebo at week 4. No changes were noted in hematology or in kidney or liver function.\n This may be the first use of the precursor strategy for a second messenger rather than a neurotransmitter in treating depression. Although inositol had a significant antidepressant effect in this study, replication is crucial.", "Some antidepressants, such as Lithium, can augment the antidepressant effect of serotonin selective uptake inhibitors (SSRI) in patients who have failed to respond to SSRI. Inositol has demonstrated antidepressant effects but in a controlled double blind augmentation trial did not improve depression in SSRI treatment failures.", "Inositol has been reported to be an effective treatment in depression, and we hypothesized that inositol addition might enhance or speed up response to serotonin selective reuptake inhibitors (SSRI).\n Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol. Hamilton Depression Rating Scale was used as an assessment tool at baseline, and 1, 2, 3, and 4 weeks.\n No significant difference was found between the two treatment groups.\n Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [e.g., monoamine oxidase inhibitors (MAOI) plus tricyclic antidepressants (TCA), TCA plus lithium]. By contrast, augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol.", "Inositol is a constituent of the intracellular phosphatidyl inositol (PI) second messenger system, which is linked to various neurotransmitter receptors. Inositol crosses the blood-brain barrier in pharmacological doses, and has shown efficacy in a small double-blind study of unipolar depression. This pilot study evaluated its potential efficacy and safety in bipolar depression.\n Twenty-four consenting adult men and women with DSM-IV bipolar depression (bipolar I = 21; bipolar II = 3) were randomly assigned to receive either 12 g of inositol or D-glucose as placebo for 6 weeks. Efficacy and safety ratings were done weekly. Thymoleptic medications (lithium, valproate, carbamazepine) in stable doses and at therapeutic levels at study entry were continued unchanged.\n Two subjects receiving placebo dropped out early due to worsening or non-adherence to the protocol. Among the 22 subjects who completed the trial, six (50%) of the inositol-treated subjects responded with a 50% or greater decrease in the baseline Hamilton Depression Rating Scale (HAM-D) score and a Clinical Global Improvement (CGI) scale score change of 'much' or 'very much' improved, as compared to three (30%) subjects assigned to placebo, a statistically nonsignificant difference. On the Montgomery-Asberg Depression Rating Scale (MADRS), eight (67%) of twelve inositol-treated subjects had a 50% or greater decrease in the baseline MADRS scores compared to four (33%) of twelve subjects assigned to placebo (p = 0.10). Inositol was well tolerated with minimal side effects, and thymoleptic blood levels were unaltered.\n These pilot data suggest a controlled study with an adequate sample size, and the appropriate rating scale may demonstrate efficacy for inositol in bipolar depression. The tolerability and the 'natural substance' aspect of inositol may be particularly appealing to subjects with bipolar depression.", "Current serotonin reuptake inhibitor (SRI) treatments for obsessive-compulsive disorder (OCD) provide only partial benefit. A previous study suggested that inositol alone is efficacious in OCD. Ten DSM-IV OCD patients completed a study of 18 g inositol or placebo for 6 wk each in addition to ongoing SRI treatment in a double-blind randomized cross-over design. Weekly assessments included the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Hamilton Depression and Anxiety scales. No significant difference was found between the two treatment phases.", "nan", "A double blind comparison is reported of a new tetracyclic antidepressant, maprotiline, with amitriptyline and placebo in psychiatric outpatients. Amitriptyline was significantly more effective than placebo in its global effect on depression. Maprotiline emerged as neither inferior to amitriptyline nor superior to placebo. Methodological difficulties prevented an adequate assessment of the anxiolytic activity of maprotiline.", "We report a randomised double blind trial of myo-inositol (inositol) supplementation for 10 days in 74 preterm infants with a birth weight less than 2000 g (mean gestational age 29.5 weeks and mean birth weight 1266 g). All infants required artificial ventilation for treatment of respiratory distress syndrome. Inositol (120-160 mg/kg/day) was administered by the ingastric or intravenous route. The 37 infants who received inositol supplementation required less mechanical ventilation during days 4-10, had less failures of indomethacin to close ductus arteriosus, and had less deaths or bronchopulmonary dysplasia, or both, than the infants treated with placebo. There were no detectable adverse effects. These preliminary results suggest that inositol is an important nutrient in immature preterm infants.", "We performed a randomized, double-blind clinical trial comparing the efficacy and safety of zimelidine with amitriptyline and placebo in outpatients with major depression, in particular patients with mixed anxiety/depressive symptomatology. Overall, amitriptyline was more effective than zimelidine and placebo after 4 weeks of treatment. However, when those patients with more severe depression were specifically examined, both antidepressants were equal in efficacy and superior to placebo. We also found no evidence for a greater likelihood of a zimelidine-induced peripheral neuropathy in this study. The present results suggest that zimelidine may be more effective in the treatment of severely depressed patients, rather than those with more mild mixed anxiety/depressive syndromes." ]

[ "9250846", "11511121", "12783106", "12971850", "17869635", "16444853", "10476589", "14675083", "15045129" ]

[ "A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group.", "A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study.", "Enoxaparin monotherapy without oral anticoagulation to treat acute symptomatic pulmonary embolism.", "[Early intravenous thrombolysis with recombinant tissue plasminogen activator for acute cerebral infarction].", "Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial.", "Extended enoxaparin monotherapy for acute symptomatic pulmonary embolism.", "Usefulness of platelet glycoprotein IIb/IIIa inhibitors in coronary stenting for reconstruction of complex lesions: procedural and 30 day outcome.", "The direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement: the EXPRESS study.", "Treatment with anticoagulants in cerebral events (TRACE)." ]

[ "Antithrombotic therapy with heparin plus aspirin reduces the rate of ischemic events in patients with unstable coronary artery disease. Low-molecular-weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, and does not require monitoring.\n In a double-blind, placebo-controlled study, we randomly assigned 3171 patients with angina at rest or non-Q-wave myocardial infarction to receive either 1 mg of enoxaparin (low-molecular-weight heparin) per kilogram of body weight, administered subcutaneously twice daily, or continuous intravenous unfractionated heparin. Therapy was continued for a minimum of 48 hours to a maximum of 8 days, and we collected data on important coronary end points over a period of 30 days.\n At 14 days the risk of death, myocardial infarction, or recurrent angina was significantly lower in the patients assigned to enoxaparin than in those assigned to unfractionated heparin (16.6 percent vs. 19.8 percent, P=0.019). At 30 days, the risk of this composite end point remained significantly lower in the enoxaparin group (19.8 percent vs. 23.3 percent, P=0.016). The need for revascularization procedures at 30 days was also significantly less frequent in the patients assigned to enoxaparin (27.1 percent vs. 32.2 percent, P=0.001). The 30-day incidence of major bleeding complications was 6.5 percent in the enoxaparin group and 7.0 percent in the unfractionated-heparin group, but the incidence of bleeding overall was significantly higher in the enoxaparin group (18.4 percent vs. 14.2 percent, P=0.001), primarily because of ecchymoses at injection sites.\n Antithrombotic therapy with enoxaparin plus aspirin was more effective than unfractionated heparin plus aspirin in reducing the incidence of ischemic events in patients with unstable angina or non-Q-wave myocardial infarction in the early phase. This benefit of enoxaparin was achieved with an increase in minor but not in major bleeding.", "ORG31540/SR90107A, a synthetic pentasaccharide, is a selective inhibitor of factor-Xa. It was hypothesized that prolonged factor-Xa inhibition with pentasaccharide may be an effective and safe antithrombotic co-therapy in acute myocardial infarction.\n Patients (n=333) with evolving ST-segment elevation acute myocardial infarction were treated with aspirin and alteplase and randomized to unfractionated heparin, given intravenously during 48 to 72 h, or to a low, medium or high dose of pentasaccharide, administered daily for 5 to 7 days, intravenously on the first day, then subcutaneously. Coronary angiography was performed at 90 min and on days 5 to 7. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 rates at 90 min were similar in the four treatment groups. Among patients with TIMI 3 flow at 90 min and who did not undergo a coronary intervention (n=155), a trend towards less reocclusion of the infarct-related vessel on days 5 to 7 was observed with pentasaccharide: 0.9% vs 7.0% with unfractionated heparin (P=0.065). Also, fewer revascularizations during the 30-day follow-up period were performed in patients given pentasaccharide (39% vs 51% for unfractionated heparin;P=0.054). The primary safety end-point, the combined incidence of intracranial haemorrhage and need for blood transfusion, was identical with pentasaccharide and unfractionated heparin (7.1%). One non-fatal intracranial haemorrhage occurred in the 241 patients given pentasaccharide (0.4%).\n In this study, pentasaccharide given together with alteplase was safe and as effective as unfractionated heparin in restoring coronary artery patency. Prolonged administration of pentasaccharide was associated with a trend towards less reocclusion and fewer revascularizations. Selective factor-Xa-inhibition seems to be an attractive therapeutic concept in patients presenting with ST-segment elevation acute myocardial infarction.\n Copyright 2001 The European Society of Cardiology.", "Conventional anticoagulation for symptomatic pulmonary embolism consists of continuous intravenous unfractionated heparin as a \"bridge\" to oral anticoagulation. This strategy requires 5 days or more of intravenous heparin while oral vitamin K antagonists gradually achieve a therapeutic effect. Oral vitamin K antagonists require frequent blood testing to optimize dosing, and their interactions with other medications and foods make regulation difficult. Therefore we tested a different approach to therapy: long-term enoxaparin monotherapy. We randomized 60 symptomatic pulmonary embolism patients in a 2:1 ratio to 90 days of enoxaparin as monotherapy without warfarin (N=40) or to intravenous unfractionated heparin as a \"bridge\" to warfarin, target INR 2.0-3.0 (N=20). Enoxaparin patients received 1 mg/kg twice daily for 14 days during the acute phase followed by randomized assignment during the chronic phase to 1.0 mg/kg vs. 1.5 mg/kg once daily. In an intention-to-treat analysis, 3 of the 40 enoxaparin patients developed recurrent venous thromboembolism compared with 0 of 20 standard therapy patients (p = 0.54). One of the 40 enoxaparin patients had a major hemorrhagic complication compared with 2 of the 20 standard therapy patients (p = 0.26). Median hospital length of stay was shorter with enoxaparin compared to standard therapy (4 vs. 6 days) (p = 0.001). Following our study we can conclude that extended 3-month treatment with enoxaparin as monotherapy for symptomatic, acute pulmonary embolism is feasible and warrants further study in a large clinical trial.", "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.", "After hip replacement surgery, prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism. Our aim was to assess the oral, direct thrombin inhibitor dabigatran etexilate for such prophylaxis.\n In this double-blind study, we randomised 3494 patients undergoing total hip replacement to treatment for 28-35 days with dabigatran etexilate 220 mg (n=1157) or 150 mg (1174) once daily, starting with a half-dose 1-4 h after surgery, or subcutaneous enoxaparin 40 mg once daily (1162), starting the evening before surgery. The primary efficacy outcome was the composite of total venous thromboembolism (venographic or symptomatic) and death from all causes during treatment. On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo, the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7%. Efficacy analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00168818.\n Median treatment duration was 33 days. 880 patients in the dabigatran etexilate 220 mg group, 874 in the dabigatran etexilate 150 mg group, and 897 in the enoxaparin group were available for the primary efficacy outcome analysis; the main reasons for exclusion in all three groups were the lack of adequate venographic data. The primary efficacy outcome occurred in 60 (6.7%) of 897 individuals in the enoxaparin group versus 53 (6.0%) of 880 patients in the dabigatran etexilate 220 mg group (absolute difference -0.7%, 95% CI -2.9 to 1.6%) and 75 (8.6%) of 874 people in the 150 mg group (1.9%, -0.6 to 4.4%). Both doses were thus non-inferior to enoxaparin. There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin (p=0.44 for 220 mg, p=0.60 for 150 mg). The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups.\n Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery, with a similar safety profile.", "We investigated the efficacy and safety of extended enoxaparin monotherapy in symptomatic patients with acute pulmonary embolism (PE). We randomized 40 patients in a 1:1 allocation to enoxaparin monotherapy (1 mg/kg twice daily for 10-18 days, and then 1.5mg/kg once daily until day 90) (n = 20) or to enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin with a target international normalized ratio of 2.0-3.0 for 90 days (at least 10 doses of enoxaparin overlapping with warfarin for at least 4 days) (n = 20). All patients underwent echocardiography, cardiac troponin I (TnI), and brain natriuretic peptide testing to identify patients with an increased likelihood of adverse clinical outcomes. The end-points were newly diagnosed deep venous thrombosis (DVT) or PE and bleeding events through day 90. In 15 patients on extended enoxaparin therapy, we used repeated measure analysis of variance (ANOVA) to investigate differences in anti-Xa levels obtained at 2, 4, 8 and 12 weeks. The patients' mean age was 52 +/- 17 years; the most common comorbidities were obesity (58%), hypertension (30%), concomitant DVT (30%) and cancer (15%). Twelve (30%) patients had elevated cardiac Tnl >0.1 mg/l and 11 (28%) had moderate or severe right ventricular dysfunction on echocardiography. Ten (25%) patients received thrombolysis with a continuous infusion of 100 mg alteplase prior to randomization. During a 90-day follow-up, one patient from the enoxaparin monotherapy group suffered symptomatic distal DVT; one from the warfarin group had recurrent symptomatic PE (p = 1.0). None of the study patients had major hemorrhage; two warfarin group patients had minor bleeding compared with none in the enoxaparin monotherapy group (p = 0.49). Repeated measure ANOVA did not reveal significant differences in anti-Xa levels over time (p = 0.217). In patients with acute symptomatic PE, extended enoxaparin monotherapy is feasible and warrants further investigation in a large clinical trial.", "Intracoronary stent implantation during percutaneous transluminal coronary angioplasty (PTCA) has shown favorable results, reducing acute complications associated with PTCA, such as coronary artery dissection and abrupt or threatened vessel closure. However, treatment of lesions with a complex morphology and diffuse disease, requiring long or multiple coronary stents, is still associated with a poorer outcome. We investigated the hypothesis that abciximab might lead to a different outcome in patients with complex coronary lesions, which require long or multiple stent implantation.\n One hundred and six patients were randomized to receive either a combination of abciximab (bolus and 12 hour infusion) and weight-adjusted low-dose heparin or weight-adjusted heparin alone and followed up to 30 days.\n The procedural success rate was 100% in both groups of patients. In the control group a composite rate of major adverse events such as any death irrespective of cause, Q wave or non-Q wave myocardial infarction, acute or subacute stent thrombosis and urgent revascularization of 15.3% was shown at 30-day follow-up. The use of abciximab reduced the composite adverse event rate to 3.7% (76% absolute reduction, p < 0.05).\n The use of abciximab during high risk stenting is safe and reduces the risk of cardiac events at 30-day follow-up as compared to standard treatment with heparin. A longer follow-up period is warranted to confirm the beneficial effects observed at 30 days with abciximab in this setting.", "Ximelagatran and its subcutaneous (s.c.) form melagatran are novel direct thrombin inhibitors for the prevention and treatment of thromboembolic disease.\n In a double-blind study, 2835 consecutive patients undergoing total hip or knee replacement were randomized to either melagatran/ximelagatran or enoxaparin. Melagatran 2 mg was started immediately before surgery; 3 mg was then administered postoperatively, followed by 24 mg of oral ximelagatran b.i.d. beginning the next day. Enoxaparin 40 mg, administered subcutaneously o.d., was started 12 h before surgery. Both treatments were continued for 8-11 days. The main efficacy outcome measures were major venous thromboembolism (VTE); [proximal deep vein thrombosis (DVT), non-fatal and/or fatal pulmonary embolism (PE), death where PE could not be ruled out], and total VTE (proximal and distal DVT; PE; death from all causes). DVT was detected by mandatory bilateral ascending venography at the end of the treatment period or earlier if clinically suspected. The main safety outcome was bleeding.\n The rates of major and total VTE were significantly lower in the melagatran/ximelagatran group compared with the enoxaparin group (2.3% vs. 6.3%, P = 0.0000018; and 20.3% vs. 26.6%, P < 0.0004, respectively). Fatal bleeding, critical site bleeding and bleeding requiring reoperation did not differ between the two groups. 'Excessive bleeding as judged by the investigator' was more frequent with melagatran/ximelagatran than with enoxaparin.\n In patients undergoing total hip or knee replacement, preoperatively initiated s.c. melagatran followed by oral ximelagatran was significantly more effective in preventing VTE than preoperatively initiated s.c. enoxaparin.", "90 patients with acute stroke and a concomitant cardiac embolism source or a symptomatic high-grade stenosis of an extra-or intracranial vessel received in a mulitcenter, randomized, controlled study either Enoxaparin 1 mg/kg BW s.c. b.i.d. or i.v. heparin aPTT-adjusted daily for 8 +/- 2 days as secondary prophylaxis. There were no significant differences between the two groups regarding cerebral and systemic embolic events, bleeding complications, length of hospital stay, number of diagnostic and therapeutic measures and outcome after three months. This suggests that Enoxaparin, which is easier to administer and monitor, is a safe drug in patients with acute cerebral events." ]

[ "11851660", "9864116", "20428997", "19816918", "11704169", "12847356", "9231856", "11744900", "15570204" ]

[ "Randomized clinical trial of laparoscopic versus open abdominal rectopexy for rectal prolapse.", "Comparison of laparoscopic rectopexy with open technique in the treatment of complete rectal prolapse: clinical and functional results.", "Anterior vaginal wall prolapse: a randomized controlled trial of SIS graft versus traditional colporrhaphy.", "Physiotherapy as an adjunct to prolapse surgery: an assessor-blinded randomized controlled trial.", "Laparoscopic Burch colposuspension: a randomized controlled trial comparing two transperitoneal surgical techniques.", "Prospective, randomized, controlled trial between a pathway of controlled rehabilitation with early ambulation and diet and traditional postoperative care after laparotomy and intestinal resection.", "Comparison of polyglycolic acid and polypropylene mesh for rectopexy in the treatment of rectal prolapse.", "Anterior colporrhaphy: a randomized trial of three surgical techniques.", "Hand-assisted laparoscopic versus open restorative proctocolectomy with ileal pouch anal anastomosis: a randomized trial." ]

[ "The objectives of this study were to compare both subjective clinical outcomes and the objective stress response of laparoscopic and open abdominal rectopexy in patients with full-thickness rectal prolapse. Abdominal rectopexy for patients with rectal prolapse is well suited for a laparoscopic approach as no resection or anastomosis is necessary.\n Forty patients with a full-thickness rectal prolapse were randomized before operation to a laparoscopic group and an open group. They agreed to conform to a clinical pathway (CP) of liquid diet (CP1) and full mobility (CP2) on day 1, solid diet (CP3) on day 2 and discharge (CP4) before day 5. Their compliance was monitored by an assessor blinded to the operative group, who also rated pain and mobility. Patient-controlled morphine use was documented. Neuroendocrine and immune stress response and respiratory function were measured.\n Some 75 per cent of all clinical pathway objectives of early recovery were achieved in the laparoscopic group compared with 37 per cent in the open group (P < 0.01). Significant differences in favour of laparoscopy were noted with regard to narcotic requirements, and pain and mobility scores. Differences in objective measures of stress response favouring laparoscopy were found for urinary catecholamines, interleukin 6, serum cortisol and C-reactive protein. No differences were noted in respiratory function but significant respiratory morbidity was greater in the open group (P < 0.05). None of the measured outcomes, subjective or objective, favoured the open group apart from operating time, which was significantly shorter (153 versus 102 min; P < 0.01).\n This study has demonstrated significant subjective and objective differences in favour of a laparoscopic technique for abdominal rectopexy. The advantages were all short term but no evidence of any adverse effect on longer-term outcomes was observed.", "The aim of this retrospective study was to compare the functional and clinical results of laparoscopic rectopexy with those of the open technique in two similar groups of patients with complete rectal prolapse and fecal incontinence. Between November 1992 and June 1997, 21 patients underwent abdominal rectopexy. Thirteen patients (group A: 12 women and 1 man, mean age 52.9 years, range 28-70) and 8 patients (group B: 8 women, mean age 58.2 years, range 20-76) were submitted to Well's rectopexy by the open technique and the laparoscopic approach, respectively, without division of the lateral rectal ligaments. Assignment to each group was done randomly. Before the operation, a detailed clinical history was taken, and patients were studied with inspection and digital examination of the anorectum, proctosigmoidoscopy, determination of pancolonic transit time, dynamic defecography, anorectal manometry, and anal electromyography. After the operation, all patients underwent perineal physiotherapy, external electric stimulation, and perineal biofeedback. The mean follow-up time was 29.5 months (range 6-54) in group A and 25.7 months (range 8-45) in group B. Values were compared by chi-square, Mann-Whitney U, and Wilcoxon tests, as appropriate; differences were considered significant at p < 0.05. In both groups, dyschezia and fecal incontinence improved significantly (p < 0.05) after the operation. Basal pressure of anal sphincter, squeezing pressure, and rectoanal reflex improved without significance, whereas anoperineal pain was not significantly reduced. In group B, the postoperative hospital stay was shorter than in group A, with a marked reduction of costs. Laparoscopic Well's rectopexy has the same clinical and functional results as the open technique, with a shorter postoperative hospital stay and lower costs.", "This study seeks to compare the small intestine submucosa (SIS) graft with traditional colporrhaphy (TC) for surgical treatment of anterior vaginal prolapse.\n Subjects were randomly assigned to SIS (n = 29) or to TC (n = 27) preoperatively and outcomes analyzed at 12 months postoperatively. The primary outcome was the absence of POP-Q stage >or= II prolapse, and secondary outcome was improvement in quality of life. Data were compared with independent samples or paired Student's t test.\n SIS group had 86.2% anatomic cure compared to 59.3% in TC (p = 0.03). SIS improved point Ba measurement significantly (-1.93 cm versus -1.37 cm, p = 0.02). Both operations significantly improved quality of life, although there were no differences between the groups. We observed a greater number of complications in the SIS group, with no infections or erosion.\n SIS repair improved point Ba significantly. However, there were no differences observed in quality of life between the techniques.", "This assessor-blinded randomized controlled trial investigated the effect of a pre- and post-operative physiotherapy-supervised pelvic floor muscle (PFM) training program in women undergoing surgery for prolapse or hysterectomy.\n Participants were assessed pre-operatively, and at 3, 6, and 12 months post-operatively by a blinded physiotherapy assessor. Following randomization, participants were allocated to a control group (CG) which included \"usual care\" (as provided by the surgeon and the hospital staff), or a treatment group (TG) which included one pre-operative and seven post-operative treatment sessions over 12 months. Primary outcomes were bladder and prolapse symptoms, measured by the Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ).\n Fifty-one participants were randomized. The 12-month post-operative findings showed there was no difference in the prevalence of the primary outcomes (ORs 1.2, 1.3). There were no significant differences between groups on the change scores of the UDI (mean: 44.1 [5.1]; 54.0 [5.4], P = 0.20) nor the IIQ (median: 0.0 [9,14]; 10.0 [5,19], P = 0.09). The repeated measures analyses also demonstrated no significant changes.\n The program tested did not improve bladder or prolapse symptoms in this trial. Reasons may include the effectiveness of surgery alone, wide variance in data, small sample size, insufficient training by the TG, and PFM training by the usual care group.\n (c) 2010 Wiley-Liss, Inc.", "To compare the effectiveness of two transperitoneal laparoscopic Burch procedures.\n The sample size required was 30 subjects per group to detect a statistically significant estimated difference of 15% between two surgical procedures with an alpha = 0.05 and a power of 0.7. Sixty women affected by genuine stress incontinence (GSI) were enrolled and randomly assigned to two groups of 30 women each. All women were treated with the transperitoneal laparoscopic Burch procedure using nonabsorbable sutures (group A) or Prolene mesh (Ethicon, Somerville, NJ) fixed with tacks or staples (group B). The failure rate was defined subjectively and objectively. The subjective evaluation was performed by asking the women to rate their urine loss on a visual analog scale. The objective evaluation was a clinical evaluation using multichannel urodynamic studies.\n The subjective failure rate was not significantly different between the two groups at 3 months (0% for both groups), 6 months (3.7% versus 3.8% for groups A and B, respectively), and 12 months (7.4% versus 15.4% for groups A and B, respectively) after surgery. At 3 months (3.7% versus 3.8% for groups A and B, respectively) and 6 months (7.4% versus 15.4% for groups A and B, respectively) follow-up, the objective failure rate was not significantly different between the two groups. However, at 12 months after the surgical procedure, the objective failure rate was significantly lower in group A than in group B (11.1% versus 26.9%, respectively; P <.05).\n Transperitoneal laparoscopic Burch colposuspension performed using sutures was more effective than the mesh technique.", "In an era of dwindling hospital resources and increasing medical costs, safe reduction in postoperative stay has become a major focus to optimize utilization of healthcare resources. Although several protocols have been reported to reduce postoperative stay, no Level I evidence exists for their use in routine clinical practice.\n Sixty-four patients undergoing laparotomy and intestinal or rectal resection were randomly assigned to a pathway of controlled rehabilitation with early ambulation and diet or to traditional postoperative care. Time to discharge from hospital, complication and readmission rates, pain level, quality of life, and patient satisfaction scores were determined at the time of discharge and at 10 and 30 days after surgery. Subgroups were defined to evaluate those who derived the optimal benefit from the protocol.\n Pathway patients spent less total time in the hospital after surgery (5.4 vs. 7.1 days; P = 0.02) and less time in the hospital during the primary admission than traditional patients. Patients younger than 70 years old had greater benefits than the overall study group (5 vs. 7.1 days; P = 0.01). Patients treated by surgeons with the most experience with the pathway spent significantly less time in the hospital than did those whose surgeons were less experienced with the pathway (P = 0.01). There was no difference between pathway and traditional patients for readmission or complication rates, pain score, quality of life after surgery, or overall satisfaction with the hospital stay.\n Patients scheduled for a laparotomy and major intestinal or rectal resection are suitable for management by a pathway of controlled rehabilitation with early ambulation and diet. Pathway patients have a shorter hospital stay, with no adverse effect on patient satisfaction, pain scores, or complication rates. Patients younger than 70 years of age derive the optimal benefit, and increased surgeon experience improves outcome.", "To compare the efficacy of absorbable and non-absorbable mesh for rectal fixation in abdominal rectopexy.\n Prospective open study.\n University hospital, Israel.\n 37 consecutive patients with complete rectal prolapse.\n Posterior abdominal rectopexy with non-absorbable mesh (Polypropylene, Prolene, Ethicon Ltd) in 17 patients and with absorbable mesh (Polyglycolic acid, Dexon, Davis & Geck) in 20.\n There was no operative mortality, and there were no significant differences between the groups in the incidence of postoperative complications. Mean (SD) follow up was 3.6(0.5) years and 3.8(0.7) years in the Dexon and Prolene groups, respectively. Preoperative and postoperative performance indices based on the Gastrointestinal Quality of Life Index were similar in both groups.\n Dexon mesh may be as effective as Prolene mesh in the treatment of complete rectal prolapse. A performance index seems to be a useful tool for evaluating the outcome of patients after repair of complete rectal prolapse.", "The purpose of this study was to compare outcomes after anterior colporrhaphy with the use of 3 different surgical techniques.\n One hundred fourteen women with anterior vaginal prolapse were randomly assigned to undergo anterior repair by one of 3 techniques: standard, standard plus polyglactin 910 mesh, or ultralateral anterior colporrhaphy. Before and after operation, patients underwent physical examination staging of prolapse; the International Continence Society system was used. Symptoms were assessed by questionnaire and visual analog scales. We defined \"cure\" as satisfactory (stage I) or optimal (stage 0) outcome at points Aa and Ba.\n Of 114 patients who were originally enrolled, 109 patients underwent operation, and 83 patients (76%) returned for follow-up. Mean age (+/- SD) was 64.7 +/- 11.1 years. At entry, 7 patients (7%) had stage I anterior vaginal prolapse; 35 patients (37%) had stage II anterior vaginal prolapse; 51 patients (54%) had stage III anterior vaginal prolapse; and 2 patients (2%) had stage IV anterior vaginal prolapse. At a median length of follow-up of 23.3 months, 10 of 33 patients (30%) who were randomly assigned to the standard anterior colporrhaphy group experienced satisfactory or optimal anatomic results, compared with 11 of 26 patients (42%) with standard plus mesh and with 11 of 24 patients (46%) with ultralateral anterior colporrhaphy. The severity of symptoms that were related to prolapse improved markedly (preoperative score, 6.9 +/- 2.7; postoperative score, 1.1 +/- 0.8). Twenty-three of 24 patients (96%) no longer required manual pressure to void after operation.\n These 3 techniques of anterior colporrhaphy provided similar anatomic cure rates and symptom resolution for anterior vaginal prolapse repair. The addition of polyglactin 910 mesh did not improve the cure rate compared with standard anterior colporrhaphy.", "The aim of the study was to evaluate postoperative recovery after hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis in a randomized controlled trial.\n Sixty patients were randomized for hand-assisted laparoscopic (n = 30) or open surgery (n = 30). Primary outcome parameter was postoperative recovery in the 3 months after surgery, measured by quality of life questionnaires (SF-36 and GIQLI). Secondary parameters were postoperative morphine requirement and surgical parameters, viz. operating time, morbidity, hospital stay, and costs.\n There was no difference between the 2 procedures in quality of life assessment in the 3 months after surgery. There was a significant decline in quality of life on all scales of the SF-36 (P < 0.001) and total GIQLI score (P < 0.001) in the first 2 weeks in both groups (no significant difference between the groups). Quality of life returned to baseline levels after 4 weeks. Operating times were longer in the laparoscopic group compared with the open group (210 and 133 minutes, respectively; P < 0.001). No significant differences were found in morphine requirement. Neither morbidity nor postoperative hospital stay differed between the laparoscopic and open group (20% versus 17%, in 10 versus 11 days, respectively). Median overall costs were 16.728 for the hand-assisted laparoscopic procedure and 13.406 for the open procedure (P = 0.095).\n Recovery measured using quality of life questionnaires is comparable for hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis. The laparoscopic approach is as safe, but more costly than the open procedure." ]

[ "15446319", "16824149", "11773888", "18089329", "9652559", "12095056", "8310508", "9921806", "9428817" ]

[ "Sequential protocols using basiliximab versus antithymocyte globulins in renal-transplant patients receiving mycophenolate mofetil and steroids.", "Two-dose basiliximab compared with two-dose daclizumab in renal transplantation: a clinical study.", "Basiliximab versus antithymocyte globulin for prevention of acute renal allograft rejection.", "Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal graft recipients.", "Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group.", "Immunoprophylaxis with basiliximab compared with antithymocyte globulin in renal transplant patients receiving MMF-containing triple therapy.", "Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. II. Results after a second kidney transplantation.", "Reduction of acute renal allograft rejection by daclizumab. Daclizumab Double Therapy Study Group.", "Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group." ]

[ "Sequential anti-thymocyte globulins (ATG)/cyclosporine immunosuppression has two main advantages: delayed introduction of the nephrotoxic drug cyclosporine and prevention of acute rejection. Basiliximab, a recently developed chimeric monoclonal antibody that selectively depletes the minor subpopulation of activated T lymphocytes, has been shown to reduce the incidence of acute rejection when used with cyclosporine introduced on day 1.\n This open, randomized, multicenter study was undertaken to compare the safety and efficacy of ATG versus basiliximab induction therapy (IT) with delayed introduction of cyclosporine for microemulsion (Neoral) in 105 low immunologic risk renal-transplant patients receiving mycophenolate mofetil and steroids.\n One-year patient and graft survival rates were 98.1% and 94.2%, respectively, in the basiliximab group (n = 52), and 98.1% and 96.2% in the ATG group (n = 53). The incidence of biopsy-confirmed acute rejection was comparable (basiliximab 9.6%, ATG 9.4%), as were key parameters of renal function, notably serum creatinine levels, time-to-nadir serum creatinine, and the number of patients requiring posttransplantation dialysis (basiliximab 28.8%, ATG 30.2%). However, significantly fewer patients in the basiliximab group experienced cytomegalovirus (CMV) infection, leukopenia, and thrombocytopenia, and this without any significant difference in any other key safety parameters (including the incidences of serum sickness, fever, lymphoma, and infections in general).\n Both ATG and basiliximab, when used for IT in a sequential protocol, are equally effective in terms of graft and patient survival as well as at preventing acute rejection. However, basiliximab is associated with a lower incidence of certain key adverse events, namely CMV infection, leukopenia, and thrombocytopenia.", "Addition of the interleukin-2 receptor (IL-2R) antagonists basiliximab or daclizumab to a calcineurin inhibitor-based regimen significantly reduces risk of acute rejection with a tolerability profile similar to a placebo. Use of a truncated two-dose regimen of daclizumab has been reported, but till date, there has been no controlled study of two-dose daclizumab vs. two-dose basiliximab.\n Deceased-donor renal transplant recipients were randomized to basiliximab (20 mg on days 0 and 4) or daclizumab (50 mg on days 1 and 14) with cyclosporine, mycophenolate mofetil and corticosteroids. Flow cytometry was used to calculate the proportion of CD25(+) T cells in peripheral blood.\n Thirty patients were randomized to basiliximab and 28 to daclizumab. There was one patient death in each group, with no other graft losses. By six months, the incidence of biopsy-proven acute rejection was 0% with basiliximab vs. 21.4% with daclizumab (p < 0.05). Three patients in the daclizumab group required OKT3 for steroid-resistant rejection. There were no between-group differences in the incidence of infection. The proportion of CD25(+) T cells declined markedly during the first two wk in both groups, but was significantly lower in the basiliximab group during weeks six to eight.\n Two doses of basiliximab are more effective than two 1 mg/kg doses of daclizumab in preventing acute rejection in de novo renal transplant patients receiving cyclosporine, mycophenolate mofetil and corticosteroid maintenance therapy. In patients receiving relatively low-level immunosuppression in order to minimize toxicity, basiliximab may be preferable to a truncated daclizumab regimen.", "Basiliximab (Simulect), a high-affinity chimeric, monoclonal antibody directed against the alpha chain of human interleukin-2 receptor (CD25), reduces the incidence of acute renal allograft rejection when used in combination with cyclosporine (Neoral) and steroids. This study was designed to compare the safety and efficacy of basiliximab to polyclonal anti-T-cell (ATGAM) therapy for the prevention of acute rejection in de novo renal transplant recipients.\n This 1-year, open-label, randomized trial was conducted in recipients of cadaveric or living-related donor renal transplants. All patients received cyclosporine (Neoral), mycophenolate mofetil (CellCept, MMF), and corticosteroids. Patients who were randomized to basiliximab therapy received a 20 mg i.v. bolus dose on days 0 and 4, and the majority of patients were initiated on cyclosporine within 48 hr of transplantation. Patients who were randomized to antithymocyte globulin therapy (ATGAM, ATG) received 15 mg/day i.v. within 48 hr of transplant and continued treatment for up to 14 days; ATG was stopped once therapeutic cyclosporine blood levels were achieved. The initiation of cyclosporine use was delayed in the ATG group until renal function was established (serum creatinine <3.0 mg/dl or 50% fall from baseline).\n Of the 138 randomized patients, 135 received at least 1 dose of study medication (70 patients, basiliximab; 65 patients, ATG). Demographic characteristics were similar between the basiliximab and ATG-treatment groups. At 12 months, the rate of biopsy-proven acute rejection was 19% and 20%, respectively, in the basiliximab and ATG groups. Although the overall profile of adverse events was similar between basiliximab- and ATG-treated patients, adverse events considered by the investigators to be associated with the study drug occurred more often among patients receiving ATG (42% vs. 11% with basiliximab).\n Basiliximab combined with early initiation of cyclosporine therapy resulted in low acute rejection rates similar to those achieved with ATG combined with delayed cyclosporine. Basiliximab therapy showed an excellent safety profile, with no increases in malignancies, infections, or deaths. Based on its convenient two-dose, body-weight independent regimen and comparable effectiveness to ATG, basiliximab is an attractive choice for the prevention of acute rejection episodes in renal transplant patients.", "In this prospective, randomized, open-label, single-center study, we compared the efficacy and safety of two anti-interleukin-2 receptor monoclonal antibodies among adult recipients of at least 1 HLA-mismatched deceased donor renal grafts. Eligible patients were randomized to induction with either basiliximab or daclizumab. Both groups received cyclosporine microemulsion (CsA Neoral), mycophenolate mofetil, and methylprednisolone. An intent-to-treat analysis of 1-year data assessed the incidence of acute rejection episodes, the renal graft function, the safety, and the patient and graft survivals. Among 127 patients, six (10.0%) and seven (11.5%) patients experienced biopsy-confirmed acute rejection at 12 months, in the basiliximab and the daclizumab groups, respectively. Two renal grafts were lost in the basiliximab and six in the daclizumab cohort, one of them due to rejection. One basiliximab and two daclizumab patients died. Hospital treatment was required for 25 and 33 infections in basiliximab and daclizumab groups, respectively. One basal cell carcinoma of skin was detected. One hypersensitivity reaction was observed with daclizumab. At 12 months, serum creatinine was 101+/-28 micromol/L with basiliximab and 109+/-41 micromol/L with daclizumab. Patient survival was 98.4% with basiliximab and 96.7% with daclizumab, and graft survival was 96.8% versus 90.8%, respectively. No significant differences were observed between the groups. Basiliximab or daclizumab combined with triple therapy was an efficient and safe immunosuppression strategy, demonstrated with low incidence of acute rejection episodes, an acceptable adverse event profile, excellent graft function, and high survival rates in adult recipients within the first year after deceased donor renal transplantation.", "Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients.\n 380 adult recipients of a primary cadaveric kidney transplant were randomly allocated, in this double-blind trial, to receive a 20 mg infusion of basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study. The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation. Safety and tolerability were monitored over the 12 months of the study.\n 376 patients were eligible for intention-to-treat analysis (basiliximab, n=190; placebo, n=186). No significant differences in patient characteristics were apparent. The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73 (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At weeks 2 and 4 post-transplantation, the mean daily dose of steroids was significantly higher in the placebo group (p<0.001 with one-way analysis of variance). The incidence of graft loss at 12 months post-transplantation was 23 (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and other adverse events was similar in the two treatment groups. The acute tolerability of basiliximab was excellent, with no evidence of cytokine-release syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%], p=0.293) occurred during the 12-month study and a further three deaths (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One post-transplantation lymphoproliferative disorder was recorded in each group.\n Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly, with no clinically relevant safety or tolerability concerns.", "Acute graft rejection remains a major problem in renal transplant recipients, and there is no consensus on the optimal immunosuppressive strategy. Immunoprophylaxis with Thymoglobulin or basiliximab has significantly reduced the incidence of acute rejection episodes and graft loss following kidney transplantation. This open, randomized, multicenter study investigated the efficacy and tolerability of basiliximab (20mg day 0-day 4) plus early cyclosporine from day 0 (n = 50) compared with Thymoglobulin plus delayed cyclosporine (n = 50) in adult kidney transplant patients. In addition, all patients received steroids and mycophenolate mofetil (MMF) at standard doses from day 0. Patient and graft survival rates at 12 months were 98 and 94% in the basiliximab group, respectively, compared with 100 and 96% in the Thymoglobulin' group. The incidences of biopsy-confirmed acute rejection (8.0% in each group) and treatment failure (14% in the basiliximab group vs. 8% in the Thymoglobulin group) were comparable in the two groups. There was a non-significant tendency to more dialysis (14 vs. 6%), and fewer cytomegalovirus (CMV) infections (p = 0.005) in the basiliximab group, but the percentage of clinical CMV was not different between the two groups (6 vs. 12%). Both strategies give excellent results, despite the differences in patterns, in nonhyperimmunized patients receiving their first cadaveric renal allograft.", "The focus of progress in transplantation immunosuppression is to achieve more specific immunosuppression with monoclonal antibodies. We have already shown that the efficacy of 33B3.1, a rat monoclonal Ig2A directed against the human IL-2 receptor, was similar to that of rabbit antithymocyte globulin in the prevention of acute rejection in first kidney transplants. A similar comparative analysis has been made in 40-sec renal transplants. ATG (1 mg/kg/day) or 33B3.1 (10 mg/day) was administered during the first 10 days postgrafting in association with corticosteroids and azathioprine. Cyclosporine was introduced on day 9 and azathioprine/CsA constituted the patient's maintenance treatment after day 45. Rejection treatment consisted of equine antilymphocyte globulin in both cases and of steroid boluses when patients were under Cyclosporine. One patient in each group died. Graft survival was 90%, 85%, and 79% in the ATG group (n = 20) and 100%, 89%, and 89% in the 33B3.1 group (n = 20) at 3, 12, and 24 months, respectively. Of the ATG group patients, 45% and 40% in the 33B3.1 group had at least one rejection episode, half the episodes in the MoAb cohort occurring under 33B3.1, vs. none in the ATG group. Transplant function was similar in both groups. Viral infections appeared to be more frequent with ATG (60%) than with 33B3.1 (12%), with CMV accounting for half of these in the ATG group, and none in the MoAb group. Tolerance of both agents was good. Of the 33B3.1 recipients, 70% developed anti-33B3.1 antibodies. From these data, we conclude that this anti-IL-2 receptor MoAb seems less effective than rabbit ATG as induction treatment in second kidney transplant patients.", "Acute rejection is still a major problem in renal transplantation and is one of the most important causes of chronic graft dysfunction and late graft loss. Selective immunosuppression with a humanized antibody against the alpha-chain of the interleukin (IL)-2 receptor (CD25) was evaluated to demonstrate the efficacy of this type of immunoprophylaxis in combination with dual immunosuppression.\n We studied the effect of daclizumab, a humanized monoclonal antibody against the alpha-chain of the IL-2 receptor, in a randomized double-blind, prospective phase III clinical trial in 275 patients receiving a first cadaveric renal allograft. Among them 111 (83%) in the placebo arm and 116 (82%) in the daclizumab arm received the full regimen of five doses (1.0 mg/kg) every other week. Baseline immunosuppression consisted of cyclosporine and corticosteroids.\n At 6 months, 39 (28%) of the patients in the daclizumab group had biopsy-proven rejections, as compared with 63 (47%) in the placebo group (P=0.001). The need for additional antilymphocyte therapy, antithymocyte globulin, antilymphocyte globulin (ATG, ALG, OKT3) was also lower in the daclizumab group (8% vs. 16%, P=0.02), and they required significantly lower mean (+/- SD) cumulative doses of prednisone (3750+/-1981 mg vs. 4438+/-2667 mg in the placebo group, P=0.01). Graft function was significantly better (P=0.02) in the daclizumab group (graft function rate: 58 vs. 51 ml/min, mean) as was patient survival (P=0.01, 99% vs. 94%). No specific adverse events were observed in daclizumab-treated patients. Patients receiving daclizumab experienced fewer cytomegalovirus infections (18% vs. 25%), and none died from severe infectious complications, compared to four patients in the placebo arm. No patient in the daclizumab group had a lymphoproliferative disorder or any other form of immunosuppression-related tumor during the first year after transplant.\n Administration of daclizumab in addition to dual immunosuppression therapy significantly reduced biopsy-proven acute rejection after renal transplantation, improved patient survival, and did not add to the toxicity of the immunosuppressive regimen.", "Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the alpha chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation.\n We administered daclizumab (1.0 mg per kilogram of body weight) or placebo intravenously before transplantation and once every other week afterward, for a total of five doses, to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine, azathioprine, and prednisone. The patients were followed at regular intervals for 12 months. The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation.\n Of the 126 patients given daclizumab, 28 (22 percent) had biopsy-confirmed episodes of acute rejection, as compared with 47 of the 134 patients (35 percent) who received placebo (P=0.03). Graft survival at 12 months was 95 percent in the daclizumab-treated patients, as compared with 90 percent in the patients given placebo (P=0.08). The patients given daclizumab did not have any adverse reactions to the drug, and at six months, there were no significant differences between the two groups with respect to infectious complications or cancers. The serum half-life of daclizumab was 20 days, and its administration resulted in prolonged saturation of interleukin-2alpha receptors on circulating lymphocytes.\n Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients." ]

[ "17461960", "8558397", "15642026", "9857596", "11966923", "15877748", "15536784", "9545899", "15101598" ]

[ "Peri-implant maintenance of immediate function implants: a pilot study comparing hyaluronic acid and chlorhexidine.", "The effect of an antiseptic mouthrinse on implant maintenance: plaque and peri-implant gingival tissues.", "Therapy of peri-implantitis with resective surgery. A 3-year clinical trial on rough screw-shaped oral implants. Part I: clinical outcome.", "Clinical and microbiologic effects of chemical versus mechanical cleansing in professional supportive implant therapy.", "Relative effectiveness of powered and manual toothbrushes in elderly patients with implant-supported mandibular overdentures.", "Treatment of peri-implantitis by the Vector system.", "Treatment of incipient peri-implant infections using topical minocycline microspheres versus topical chlorhexidine gel as an adjunct to mechanical debridement.", "Effects of subgingival chlorhexidine irrigation on peri-implant maintenance.", "Cemented versus screw-retained implant-supported single-tooth crowns: a 4-year prospective clinical study." ]

[ "In implants, maintenance assumes an important role. The role of chlorhexidine (CHX) is well known in maintenance, while only limited evidence exists on the practical use of hyaluronic acid (HA). The objective of this study was to compare the health status of the peri-implant complex (hard and soft tissues surrounding the implant) during the healing period of immediate function implants, using HA or CHX gels in the patient's maintenance protocol. STUDY POPULATION AND METHODOLOGY: Thirty complete edentulous patients, with four immediate function Brånemark System implants placed in the mandible (total of 120 implants), were randomly assigned to two groups (HA and CHX) using only these two chemicals in their daily implant self-care. Both groups were followed up for 6 months, with clinical observations on the 10th day, 2 months, 4 months and 6 months post-surgically.\n During the course of the study, HA and CHX produced good results in maintaining a healthy peri-implant complex in immediate function implants for complete rehabilitations in the edentulous mandible. Statistically significant differences were found in favour of the HA group in the modified bleeding index on the second observation (P = 0.003). The difference was more marked in the axial implants placed in the fifth sextant (P = 0.05). Correlation coefficient between plaque and bleeding index revealed a potentially better result for CHX at 6 months.\n The findings point out the importance of a maintenance protocol in immediate function implants. Both chemicals are valid tools for implant maintenance. The authors suggest that it might be advantageous to administer HA in the first 2 months and CHX between 2 and 6 months.", "The purpose of this controlled double-blind, parallel, randomized clinical study was to determine the effect of antiseptic mouthrinse on parameters important to dental implant maintenance. Plaque, peri-implant gingivitis, gingival bleeding, probing depth, and attachment level were assessed over a 3-month test period. Twenty healthy adult patients each of whom had at least two dental implants, a modified gingival index > 1.5, and a modified Quigley-Hein plaque index score > 1.7 were enrolled into the study. After a thorough oral prophylaxis, patients were randomly assigned to either the antiseptic mouthrinse or a 5% hydroalcohol placebo mouthrinse group and instructed to rinse twice daily for 30 seconds with 20 ml of their assigned mouthrinse as an adjunct to their usual oral hygiene procedures. The baseline examination included plaque index, gingival index, bleeding index, probing depth measurement, and attachment level measurements. The plaque and gingival indices were rescored at 1, 2, and 3 months. Probing depths, attachment levels, and bleeding index were determined again at 3 months only. At the end of 3 months, the antiseptic mouthrinse group had statistically significant reductions in plaque index, gingival index, and bleeding index compared to the placebo group. There were no significant differences between groups in probing depth or attachment level. The results of this clinical study indicate that twice daily use of an antiseptic mouthrinse may provide benefits in the maintenance of dental implants.", "The purpose of this randomized clinical trial was to compare the clinical outcome of two different surgical approaches for the treatment of peri-implantitis. Seventeen patients with ITI(R) implants were included consecutively over a period of 5 years. The patients were randomized with a lottery assignment. Ten patients were treated with resective surgery and modification of surface topography (test group). The remaining seven patients were treated with resective surgery only (control group). Clinical parameters (suppuration, modified plaque index - mPI, modified bleeding index - mBI, probing pocket depth - PPD, pseudopocket - DIM, mucosal recession - REC, probing attachment level - PAL) were recorded at baseline, as well as 6, 12, 24 and 36 months after treatment. The cumulative survival rate for the implants of the test group was 100% after 3 years. After 24 months, two hollow-screw implants of control group were removed because of mobility. Consequently, the cumulative survival rate was 87.5%. The recession index in the control group was significantly lower than in the test group at 24 months (Student's t-value of -2.14). On the contrary, control group showed higher PPD, PAL and mBI indexes than test group (Student's t-values of +5.5, +2.4 and +9.61, respectively). The PPD and mBI indexes for the implants of the control group were significantly higher at baseline than 24 months later (Student's t-values of +3.18 and +3.33, respectively). Recession and PAL indexes resulted in values significantly lower than baseline (Student's t-values of -4.62 and -2.77, respectively). For the implants of the test group PPD and mBI indexes were significantly higher at baseline than 36 months after (Student's t-values of +11.63 and +16.02, respectively). Recession index resulted in values significantly lower at baseline (Student's t-value of -5.05). No statistically significant differences were found between PAL index measurement at baseline and 36 months later (Student's t-value of +0.89). In conclusion, resective therapy associated with implantoplasty seems to influence positively the survival of oral implants affected by inflammatory processes.", "The aim of the present study was to compare the cleansing properties of mechanical supportive care for dental implants with the use of an etching gel. Sixteen patients underwent a 5-month clinical trial with monthly recalls. These patients, wearing maxillary complete dentures and mandibular overdentures supported by a bar device on 4 implants, were treated in a split-mouth study design. Test and control therapy were randomly assigned to left and right sides of the mandible. At the test side, 35% phosphoric etching gel (pH 1) was applied in the peri-implant sulcus. After 1 minute, the sulcus was thoroughly rinsed with a water spray for approximately 15 seconds per implants. Control therapy consisted of supra- and subgingival debridement using carbon fiber curettes and a rubber cup. Plaque, calculus, probing pocket depth, and modified Gingival Index were determined before each treatment. Microbiologic evaluation was performed at baseline, 1 month later, and 5 months later, just before and immediately after each treatment. Per treatment and per assessment, the mean scores of all clinical parameters were calculated for each patient. The number of colony-forming units was used as the primary efficacy variable in the analysis of microbiologic data. At baseline, no differences between test and control sites were observed for any of the clinical parameters. The mean Gingival Index and the mean probing pocket depth were reduced over the 5-month period. The mean reduction in Gingival Index at the test sites proved to be significantly larger at the control sites (P = .03). Both treatment modalities resulted in an instant reduction of the number of colony-forming units, where the reduction by chemical cleaning was larger (P < .05). This short-term study employing a high recall frequency indicates that local application of 35% phosphoric acid gel can be as effective as conventional mechanical supportive therapy.", "The aim of this study was to compare the clinical effectiveness of a powered toothbrush (Braun Oral-B Plaque Remover 3-D) and a manual soft toothbrush (Oral-B Squish-grip brush) for the control of supragingival plaque and soft tissue inflammation around implants supporting mandibular overdentures.\n The study sample involved 40 edentulous subjects, aged 55-80 years, having 2 unsplinted mandibular implants supporting a complete removable overdenture opposed by a maxillary complete denture. In this single-blinded, randomised, cross-over clinical trial, two 6-week experimental phases were separated by a 2-week wash-out period. 2 weeks prior to each experimental phase (pre-entry visits), implant abutments were polished to remove all plaque and a standardised instruction in the use of the toothbrush was given. Modified plaque and bleeding indices were recorded at the start and end of each experimental period. Mean index scores at each phase were analysed using paired t-test, and the mean number of sites showing a change in plaque or mucositis were compared using the Mann-Whitney U-test. Combined data from 2 different implant systems were considered after controlling for implant type.\n Only minor changes in plaque and bleeding scores were observed following the two test periods. There were no statistically significant differences between the manual and powered toothbrushes.\n Manual and powered brushes were found to be of comparable efficacy with regard to improvement in peri-implant bleeding and plaque indices.", "To compare the effectiveness of treatment of peri-implantitis with a novel ultrasonic device, the Vector system, with that of subgingival debridement with carbon fiber curettes.\n The study, comprising 11 patients with at least two screw type implants with bleeding on probing (BOP), probing pocket depth (PPD) > or =5 mm, and at least 1.5 mm radiographic bone loss and exposed implant threads, was carried out as a single blind randomized clinical trial. At baseline one randomly chosen implant in each patient was treated by the Vector system (test) while the other implant (control) was treated by submucosal debridement with a carbon fiber curette. After 3 months, the same treatments were repeated. Plaque, BOP, and PPD were recorded on all implant surfaces at baseline, and after 3 and 6 months. Bone levels were recorded on radiographs taken prior to the start of the study, and after 6 months.\n Oral hygiene around both test and control implants was improved at 3 and 6 months compared with baseline. At 6 months, four of the Vector-treated sites, and only one site treated with curettes, had stopped to bleed. In neither the test nor the control group, were there any differences between baseline and 6 months regarding PPD and bone levels.\n Although there was a greater reduction in the number of sites with BOP following treatment with the Vector system than following instrumentation with carbon fiber curettes, there was no significant difference between the two methods.", "This report presents the clinical results three months after application of minocycline microspheres as an adjunct to mechanical treatment of incipient peri-implant infections compared to adjunctive treatment employing 1% chlorhexidine gel application. Sixteen patients in the minocycline group and 14 in the chlorhexidine group completed the study. Each patient had one or more implants with probing depth > or = 4 mm combined with bleeding and/or exudate on probing and presence of putative pathogenic bacteria. At baseline, patients were randomly assigned to minocycline or chlorhexidine treatment. Follow-up examinations were carried out after 10, 30, 60 and 90 days. The combined mechanical/antimicrobial treatment for the chlorhexidine group did not result in any reduction in probing depth and only limited reduction of bleeding scores. The adjunctive use of minocycline microspheres, on the other hand, resulted in improvements in both probing depths and bleeding scores. For the deepest sites of the treated implants, mean probing depth was reduced from 5.0 mm to 4.1 mm. The reductions in bleeding scores, although greater than for the chlorhexidine group, were modest. Thus, the question as to what extent the combined mechanical/minocycline treatment could be considered adequate for the treated lesions remains to be answered. The present short-term findings, however, encourage further studies with longer observation intervals on adjunctive use of minocycline microspheres in the treatment of periimplant lesions.", "To evaluate the effect of irrigation with 0.06% chlorhexidine (PerioGard) (CHX) using a powered oral irrigator (Water Pik) with a special subgingival irrigating tip (Pik Pocket Subgingival Tip) compared to rinsing with 0.12% chlorhexidine gluconate once daily.\n Following a prophylaxis, patients were randomly assigned to an irrigation or a rinse group. The following clinical parameters were measured at baseline and at the 3-month end of the study: Modified Gingival Index (MGI), Plaque Index (PI), Bleeding Index (BI), and Calculus Index (CI). Also, a Stain Index (SI) was measured at 3 months.\n Patients irrigating with diluted CHX showed a statistically significant reduction (P < 0.05) from their baseline in the MGI, PI, BI, and CI scores at 3 months. In the rinse group both MGI and BI showed statistically significant reduction from their baseline (P < 0.05) at 3 months. The rinse group showed a nonsignificant (P > 0.05) increase from baseline in CI and a nonsignificant decrease in PI. Intergroup comparisons showed that CHX irrigation produced statistically significantly greater reductions than CHX rinsing in the PI, MGI, and SI. The irrigation group also showed a greater reduction in BI and CI than the rinsing group but these differences were not statistically significant (P = 0.12). The results of this study suggest that use of diluted 0.06% CHX when used in a powered irrigator may be a valuable adjunct to oral health in patients with implants.", "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." ]

[ "8445463", "11302304", "11841372", "15160576", "8894860", "3063436", "8886085", "11826641", "11737438" ]

[ "Use of sodium hyaluronate in treating temporomandibular joint disorders: a randomized, double-blind, placebo-controlled clinical trial.", "Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group.", "Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel.", "An evaluation of Hyalofill-F plus compression bandaging in the treatment of chronic venous ulcers.", "Hyaluronidase (Hyalase): a useful addition in haematoma block?", "Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee.", "High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial.", "[Randomized controlled trial of sodium hyaluronate for degenerative disorders of the temporomandibular joint].", "Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses." ]

[ "This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporomandibular joint (TMJ) disorders. One hundred twenty-one patients were studied at three test sites using a randomized, double-blind, placebo-controlled experimental design. Patients were selected on the basis of 1) confirmed diagnosis of either degenerative joint disease (DJD), reducing displaced disc (DDR), or nonreducing displaced disc (DDN); 2) nonresponsiveness to nonsurgical therapies; and 3) severe dysfunction as established by the Helkimo indices (HI), visual analog scales (VASs), and physical measurements of joint movement and joint noise (arthrophonometry [APM]). Subjects received a unilateral upper joint space injection of either 1) 1% sodium hyaluronate in physiologic saline (MedChem Products, Woburn, MA) or 2) USP physiologic saline. Clinical evaluations were performed using HI, VAS, and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection. Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval. For DJD, no difference in outcome was seen between treatment groups. For DDN, significant between-group differences were seen through 1 month; however, beyond this time point, the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy. For DDR, statistically significant within-group and between-group improvement in all three measures (HI, VAS, APM) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period. At the month-2 and month-3 examination intervals, twice as many patients treated with hyaluronate (90%) showed improvement compared to patients given placebo. Further, only 3% of patients with DDR who were treated with hyaluronate relapsed compared with 31% of patients with DDR given placebo.", "A prospective, multicenter, randomized, double-blind, controlled trial was conducted in 226 patients with knee osteoarthritis to evaluate the safety and efficacy of intraarticular injections of sodium hyaluronate. Patients were randomized to three weekly injections of 30 mg sodium hyaluronate or physiologic saline (control) and were observed for an additional 25 weeks. In comparison with the control group, among patients who completed at least 15 weeks of the study and whose Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was less than 12 at baseline, sodium hyaluronate injection resulted in improvement in Western Ontario and McMaster Universities Osteoarthritis Index pain score, patient and investigator global assessments, and pain on standing from Weeks 7 to 27. Fifty-eight percent of patients treated with sodium hyaluronate achieved a 5-unit or greater improvement in mean pain score from Weeks 7 through 27, compared with 40% of control patients. In addition, nearly twice as many patients treated with sodium hyaluronate as with saline (30% versus 17%, respectively) achieved a net improvement of at least 7 units. In contrast to treatment with saline, Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was inversely related to the magnitude of improvement after treatment with sodium hyaluronate. Few side effects were attributed to treatment, and no differences between treatment groups were seen in this respect (sodium hyaluronate, nine [8%]; saline, 11 [10%]). The incidence of injection site reactions was low (sodium hyaluronate, 1.2 %; saline, 1.5%). The results indicate that sodium hyaluronate treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee osteoarthritis in whom pain in the contralateral knee is relatively modest.", "Actinic keratoses (AKs) are premalignant skin lesions, which, if left untreated, can develop into squamous cell carcinoma. Current treatments for AKs are destructive and are often associated with significant adverse events. The development of an effective and well-tolerated topical treatment for AK is desirable.\n To evaluate the efficacy and safety of 3.0% diclofenac in 2.5% hyaluronan gel as a treatment for AK.\n This was a multicentre, double-blind, placebo-controlled study in which 195 patients with at least five AKs in up to three designated treatment blocks were randomized to four treatment groups. Patients randomized into the active treatment groups A30 (n = 49) and A60 (n = 48) received topical treatment with 3.0% diclofenac in 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Patients in the placebo (vehicle gel) groups V30 (n = 49) and V60 (n = 49) received topical treatment with 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Treatment efficacy was assessed by target and cumulative lesion number scores (TLNS and CLNS, respectively) and lesion total thickness score (TTS). Investigator and patient global improvement indices (IGII and PGII) were also used to rate overall improvement.\n Compared with placebo, significantly more patients given active treatment for 60 days had TLNS = 0 (33% vs. 10%, P < 0.05; an improvement of 64% compared with 34% with placebo), CLNS = 0 (31% vs. 8%, P < 0.05; an improvement of 54% compared with 23% with placebo) and TTS = 0 (25% vs. 6%, P < 0.05; an improvement of 59% compared with 31% with placebo). The IGII and PGII scores were also significantly better when active treatment was compared with placebo (P < 0.05). Both treatments were generally well tolerated and the incidence of the most common adverse events was similar between groups.\n Treatment with 3.0% diclofenac in 2.5% hyaluronan gel was effective when used for 60 days and was well tolerated in patients with AK.", "Hyaluronan, a component of the extracellular matrix, plays a significant role in several aspects of tissue repair and the wound healing process.\n In this Italian study Hyalofill-F, a partial benzyl ester derivative of hyaluronan, used in combination with compression bandaging, was compared with the well-established therapy in Italy of non-adherent gauze plus compression therapy in the treatment of chronic venous leg ulcers.\n Hyalofill-F plus compression bandaging performed significantly better than non-adherent gauze plus compression bandage in all of the clinically relevant efficacy parameters. Mean reduction in ulcer area in the hyaluronan-derivative group was 8.1 cm2 after eight weeks of treatment, compared with 0.4 cm2 in the comparator group. The resulting difference of 7.7 cm2 between the two groups was statistically significant (p = 0.0019). Furthermore, statistically significant results in favour of the hyaluronan-derivative group were obtained in the following: speed of epithelialisation; leveling of the margins; degree of maceration; pain intensity and frequency.\n Hyalofill-F plus compression bandaging resulted in an earlier and greater decrease in ulcer area compared with non-adherent gauze plus compression bandaging, therapy supporting its use in the treatment of chronic venous ulcers.", "To investigate whether hyaluronidase (Hyalase) is a useful and justified addition to haematoma block for pain relief.\n The study was a randomised double blind trial of 33 consecutive patients attending the accident and emergency department for manipulation of distal radius fracture under haematoma block. Control patients received 1% lignocaine; the treatment group received 1% lignocaine plus 1500 IU hyaluronidase. Manipulation occurred 10 minutes after instituting the block.\n 16 patients received hyaluronidase, 17 received lignocaine only. One patient with unsuccessful manipulation was excluded. There was no significant difference between the two groups for any of three methods of pain assessment (P > 0.05, Mann Whitney).\n The addition of hyaluronidase does not increase the efficacy of the haematoma block when 10 minutes are allowed to elapse before manipulation, and the increased cost of adding (and risk of allergy) is not justified by any theoretical increased speed of analgesia.", "A multi-centre randomized, double-blind, parallel-group clinical trial was carried out in 63 patients with osteoarthritis of the knee to compare the efficacy and tolerability of a course of intra-articular injections of 20 mg sodium hyaluronate with a similar course of injections of placebo. Treatment consisted of up to 11 injections over a 23-week period. Evaluation was by means of subjective symptom and activity assessments, serially during the course of treatment and also 25 weeks thereafter. Ten patients (5 of 30 on active treatment; 5 of 33 on placebo) were withdrawn prematurely. Pain on movement, assessed by visual analogue scale (VAS) showed statistically significant (p less than 0.05 to p less than 0.0001) reductions in mean scores throughout the first 11 weeks of treatment with sodium hyaluronate but smaller, non-significant, reductions with placebo treatment. The difference between treatments was significant (p less than 0.05) at 5 weeks. Pain at rest, also assessed by VAS, showed little change in mean scores with placebo but with sodium hyaluronate there was a progressive reduction which was significant (p less than 0.01) throughout the period from 5 to 23 weeks. The difference between sodium hyaluronate and placebo was significant (p less than 0.05 to p less than 0.002) at Weeks 5, 11, 15, 19 and 23. 'Activities of daily living' were assessed using a standard scale. There were small improvements with both treatments, significant at some assessments and somewhat greater with sodium hyaluronate than placebo, but there were no statistically significant differences between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks' combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years' duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: -35.5 +/- 26.4 mm vs -25.8 +/- 21.4, P = 0.03, Lequesne's functional index: -3.8 +/- 4.3 vs -2.3 +/- 3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician's overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (-4.4 +/- 5.1 vs -2.7 +/- 4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee.", "To assess the effect of sodium hyaluronate (HA) for degenerative disorders of the temporomandibular joint (TMJ).\n A prospective randomized controlled clinical trial was conducted. The experimental group received injections in the upper compartments of the involved TMJs with 1% HA 6 mg, whereas the control group received prednisolone (PS) 12.5 mg once a week. Three to four injections were as one course. Before and one week after the treatment courses, clinical symptoms, amount of interleukin-6 (IL-6) and total protein of synovial fluid were measured and compared.\n Sixty-seven patients were included and 4 out of them were dropped out. There were 12 males and 51 females, among them, 14 cases with synovitis, 21 with anterior disc displacement without reduction and 28 with osteoarthritis of the TMJ. Thirty-five patients allocated in HA group and 28 in PS group. Both drugs could relieve the clinical symptoms of TMJ degenerative disorders. In HA group, marked improvement rate was 51.43% and failure rate was 2.86%, whereas marked improvement rate 39.29% and failure rate 17.86% in PS group. The declined levels of IL-6 in synovial fluid was notably greater in HA group than those in PS group.\n Intra-articular injection of HA is effective and safe to treat TMJ degenerative disorders with mild adverse reactions, better in terms of effective rate and declined level of IL-6 than PS.", "Actinic keratoses (AKs) are epidermal skin lesions with the potential to develop into invasive squamous cell carcinoma (SCC). Treatment at an early stage may prevent development of SCC. Current treatment options are highly destructive and associated with significant side-effects. Early studies with topical diclofenac were encouraging and led to its evaluation for the treatment of actinic keratosis. Previous studies have demonstrated that 3% diclofenac in 2.5% hyaluronan gel is effective and well tolerated in the treatment of AK. The present study was designed to further explore the therapeutic potential of this gel.\n This randomized, double-blind, placebo-controlled trial involved outpatients with a diagnosis of five or more AK lesions contained in one to three 5 cm(2) blocks. Patients received either active treatment (3% diclofenac gel in 2.5% hyaluronan gel) or inactive gel vehicle (hyaluronan) as placebo (0.5 g b.i.d. in each 5 cm(2) treatment area for 90 days). Assessments included the Target Lesion Number Score (TLNS), Cumulative Lesion Number Score (CLNS), and Global Improvement Indices rated separately by both the investigator (IGII) and patient (PGII).\n Results obtained from 96 patients at follow up (30 days after end of treatment) indicated that a significantly higher proportion of patients who received active treatment had a TLNS = 0 compared to the placebo group (50% vs. 20%; P < 0.001). There was also a significant difference between the two groups in CLNS, with 47% of patients in the active treatment group having a CLNS = 0 compared with only 19% in the placebo group (P < 0.001). The proportion of patients with an IGII score of 4 (completely improved) at follow-up was 47% in the active treatment group compared with only 19% in the placebo group (P < 0.001); for PGII these values were 41% vs. 17%, P < 0.001. Both treatments were well tolerated, with most adverse events related to the skin.\n Topical 3% diclofenac in 2.5% hyaluronan gel was effective and well tolerated for the treatment of AK." ]

[ "12745558", "16616557", "16641396", "3755517", "15695996", "10837300", "20215360", "11086300", "2587133" ]

[ "A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour.", "Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.", "Vitamins C and E and the risks of preeclampsia and perinatal complications.", "Vitamin D supplementation in pregnancy: a controlled trial of two methods.", "Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial.", "Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal.", "Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial.", "Vitamin a status of pregnant women and effect of post partum vitamin a supplementation.", "Maternal administration of vitamin K does not improve the coagulation profile of preterm infants." ]

[ "In a previous study from this institution, patients at high risk for preterm labour were screened for the presence of bacterial vaginosis (BV). When BV was present, they were randomised to receive either treatment (metronidazole) or placebo (vitamin C). There were significantly more patients with preterm labour in the metronidazole group. The aim of this double-blind randomised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour. Patients with a history of preterm labour in a preceding pregnancy were randomised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks' gestation. They attended a dedicated premature labour clinic. Significantly more women delivered before term in the group that received vitamin C, but there was no difference in the outcome of the babies between the two groups. Supplementation with vitamin C did not prevent premature labour.", "Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors.\n We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 .\n Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]).\n Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.", "Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.\n We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.\n Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).\n Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).\n Copyright 2006 Massachusetts Medical Society.", "A randomized study was conducted to evaluate the effects of single-dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France. The women were divided into three randomized groups: one (N = 21) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy, one (N = 27) was given a single oral dose of 5 mg at the seventh month of pregnancy, and one (N = 29) acted as a control. Venous plasma samples were obtained at delivery from the women and from cord blood, and levels of calcium, 25-OHD, and 1,25(OH)2D were determined. No significant difference in plasma calcium concentration was found among the three groups, but within each group plasma calcium concentrations were higher in the cord samples than in the respective maternal samples. The levels of the two metabolites measured were consistently lower in the cord samples than in the respective maternal samples. Cord 25-OHD concentrations correlated with those of maternal plasma. No significant modification of maternal calciuria or of the birth weight of term infants was observed. 25-OHD concentrations were greater in maternal and cord plasma from treated mothers, but only a slight difference was observed between the supplemented groups. 1,25(OH)2D concentrations were not significantly different in the three groups. A single 5-mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors' region.", "We sought to determine the effect of supplemental antioxidant vitamins C and E on the rate of preeclampsia in high-risk pregnant women.\n Women at risk for preeclampsia (previous preeclampsia, chronic hypertension, pregestational diabetes, or multifetal gestation) were recruited at 14 to 20 weeks' gestation and randomly assigned to receive either 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily in addition to their regular prenatal vitamins. The primary outcome was the occurrence of preeclampsia. An estimated sample size of 220 women in each arm was determined to be necessary to demonstrate a 50% reduction in the rate of preeclampsia.\n Funding was terminated after 109 women had been recruited; 9 were lost to follow-up or withdrew. We analyzed data from the remaining 100 women to look for differences in outcome and to estimate the required sample size for future studies. The rate of preeclampsia was not different: 17.3% in women who received supplemental vitamins C and E, versus 18.8% in the placebo group. Assuming a baseline rate of preeclampsia in the placebo group between 15% and 20%, we can estimate that 500 to 950 women in each arm will be required to show a clinically important reduction in the rate of preeclampsia.\n The potential benefit of vitamin C and E supplementation to prevent preeclampsia in women with clinical risk factors is smaller than we estimated. Future studies of antioxidant vitamin supplementation in this population will require more than 500 women in each arm.", "The effect of vitamin A supplementation on the survival of infants aged <6 mo is unclear. Because most infant deaths occur in the first few month of life, maternal supplementation may improve infant survival.\n The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants <6 mo of age.\n Married women of reproductive age in 270 wards of Sarlahi district, Nepal, were eligible to participate. Wards were randomly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate (vitamin A), 42 mg all-trans-beta-carotene, or placebo. Pregnancies were followed until miscarriage, stillbirth, maternal death, or live birth of one or more infants, who were followed through 24 wk of age.\n A total of 43559 women were enrolled; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial. The rate of fetal loss was 92.0/1000 pregnancies in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.06 (95% CI: 0.91, 1.25) and 1.03 (95% CI: 0.87, 1.19), respectively. The 24-wk mortality rate was 70.8/1000 live births in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.05 (95% CI: 0.87, 1.25) and 1.03 (95% CI: 0.86, 1.22), respectively.\n Small weekly doses of vitamin A or beta-carotene given to women before conception, during pregnancy, and through 24 wk postpartum did not improve fetal or early infant survival in Nepal.", "To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates.\n Randomised, placebo controlled, two by two factorial trial.\n Bissau, Guinea-Bissau.\n 1717 low birthweight neonates born at the national hospital.\n Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12 months.\n Mortality, calculated as mortality rate ratios (MRRs), after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo.\n No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to \"early BCG\" versus \"no early BCG\" was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046), the MRR of vitamin A supplementation being 0.74 (95% CI 0.45 to 1.22) in boys and 1.42 (95% CI 0.94 to 2.15) in girls. When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau, the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 (95% CI 0.87 to 1.33); 0.80 (95% CI 0.58 to 1.10) in boys and 1.41 (95% CI 1.04 to 1.90) in girls (P=0.01 for interaction between neonatal vitamin A and sex).\n The combined results of this trial and the complementary trial among normal birthweight neonates have now shown that, overall, it would not be beneficial to implement a neonatal vitamin A supplementation policy in Guinea-Bissau. Worryingly, the trials show that vitamin A supplementation at birth can be harmful in girls. Previous studies and future trials should investigate the possibility that vitamin A supplementation has sex differential effects. Trial registration ClinicalTrials.gov NCT00168610.", "To assess the Vitamin A status of pregnant women in their third trimester using maternal serum retinol levels as the indicator; and (ii) To assess the impact of postpartum Vitamin A supplementation on the Vitamin A status of exclusively breastfed infants.\n Prospective randomized single blind controlled study.\n Teaching Hospital.\n 109 apparently healthy primi and second gravida women registered at the antenatal clinic were included in the study and followed up for three months postpartum. Serum retinol levels of pregnant mothers in their third trimester (35-37 weeks) and cord blood levels after delivery were estimated. Mothers were then assigned to two groups. The experimental group included 53 mothers who received a single dose of 2 lakh units of Vitamin A orally. The control group had 56 mothers who did not receive Vitamin A. Mothers and infants were followed up for three months. The serum retinol of infants and the breast milk retinol levels were estimated at the end of three months and the results were compared. The growth of the infants was also monitored.\n Subclinical Vitamin A deficiency was seen in 29.67% of pregnant women. At the end of three months, 69.6% of mothers in the control group had breast milk retinol levels below 30 mg/dl, as opposed to 36.1% in the experimental group. Forty five per cent of infants in the control group had subclinical vitamin A deficiency compared to none in the experimental group. There was no difference in the growth of infants in the two groups. However, the infant serum and the breast milk retinol levels were significantly higher in the supplemented group.\n There is a high prevalence of inapparent Vitamin A deficiency (29.7%) in pregnant women in their third trimester from lower socio-economic strata. Postpartum Vitamin A supplementation had a beneficial impact on the infant serum retional and the breast milk retinol level but no effect on infant growth.", "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." ]

[ "9024451", "16877299", "11789240", "11006365", "12926838", "9301350", "8621174", "12525716", "11313301" ]

[ "Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis.", "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.", "[Effect of Tripterygium polyglycoside on interleukin-6 in patients with Guillain-Barre syndrome].", "Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group.", "Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study.", "Randomised controlled trial of inhaled corticosteroids (fluticasone propionate) in cystic fibrosis.", "A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C.", "Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial.", "Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis." ]

[ "To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).\n Prospective, controlled, randomized study.\n Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.\n No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.\n Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly.", "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.", "To study the action of interleukin-6(IL-6) in pathogenesis and effect of patients with Guillain-Barre syndrome (GBS).\n Forty-three patients of GBS were selected according to Asbury's standard and divided into two groups on layer randomize principle, they were treated with adrenal corticosteroid and Tripterygium polyglycoside (TP) respectively. Serum and cerebrospinal fluid (CSF) content of IL-6 were measured by double antibody sandwich ELISA method.\n (1) The serum and CSF content of IL-6 in GBS group was higher than those in the normal control group significantly; (2) There was positive correlation between CSF IL-6 and clinical severity (P < 0.01) before treatment; (3) After treatment the clinical symptoms were improved in both groups, but the TP treated group showed better effect than the control group in improving symptoms and lowering serum IL-6 level (P < 0.05).\n CSF level of IL-6 could be taken as one of the criteria for severity evaluation of patient's condition. TP is superior in suppressing abnormal immune reaction to adrenal corticosteroid in GBS patients.", "Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value.\n We conducted a randomized, double-blind trial of 383 patients who had a first acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or brain-stem or cerebellar syndrome) and evidence of prior subclinical demyelination on magnetic resonance imaging (MRI) of the brain. After initial treatment with corticosteroids, 193 patients were randomly assigned to receive weekly intramuscular injections of 30 microg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo. The study end points were the development of clinically definite multiple sclerosis and changes in findings on MRI of the brain. The trial was stopped after a preplanned interim efficacy analysis.\n During three years of follow-up, the cumulative probability of the development of clinically definite multiple sclerosis was significantly lower in the interferon beta-1a group than in the placebo group (rate ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.002). As compared with the patients in the placebo group, patients in the interferon beta-1a group had a relative reduction in the volume of brain lesions (P<0.001), fewer new or enlarging lesions (P<0.001), and fewer gadolinium-enhancing lesions (P<0.001) at 18 months.\n Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinically definite multiple sclerosis.", "Interferon beta (IFNB) is available in parenteral formulations for treatment of multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients.\n In this multicenter; double-blind randomized trial, RR-MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. Gadolinium DTPA-enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients.\n Of 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. Adverse events showed no notable group differences. Approximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups.\n Oral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated.", "Controlling lung inflammation may be the key to improving morbidity and mortality in cystic fibrosis.\n To assess the effects of inhaled corticosteroids on lung inflammation in cystic fibrosis.\n Double blind placebo controlled randomised sequence crossover trial. Fluticasone propionate (400 micrograms/day) was given as a dry powder inhaler for six weeks with a four week washout period before crossover.\n Sputum inflammatory markers (interleukin-8, tumour necrosis factor-alpha (TNF-alpha) and neutrophil elastase-both free and bound to alpha 1-antiprotease), sputum interleukin-10, lung function, and symptomatology.\n Twenty three children from a regional cystic fibrosis centre were enrolled into the study, with mean age 10.3 years (range 7 to 17 years) and mean baseline forced expiratory volume in one second (FEV1) of 64% (range 21% to 102%) predicted for sex and height. One patient was excluded for non-compliance to the study protocol.\n No significant benefit was shown for the use of fluticasone propionate in any of the outcomes. For sputum interleukin-8 there was an estimated true treatment median difference of 142 pg/ml (95% confidence interval (CI) 8 to 2866 pg/ml) in favour of placebo; while for maximal expiratory flow at 25% (MEF25%) remaining forced vital capacity predicted for sex and height there was a 15 percentage points (pp) (95% CI 4 to 26 pp) mean treatment difference in favour of placebo. Sputum interleukin-10 was undetected in any samples and unaffected by fluticasone propionate. Neither atopic status, baseline FEV1, nor concomitant DNase therapy had any effect on response to treatment.\n Lack of benefit from fluticasone propionate was most likely due to failure of the drug to penetrate the viscid mucus lining the airways. It is suggested a large multicentre trial with higher doses given for a longer time by a different delivery system is required to assess efficacy.", "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.", "Patients with primary progressive MS have atypical clinical and MRI characteristics and have been excluded from most therapeutic trials. The authors report a randomized, controlled trial restricted to primary progressive MS.\n Fifty subjects were randomized to weekly IM interferon beta-1a 30 microg, 60 microg, or placebo for 2 years. The primary endpoint was time to sustained progression in disability. Secondary outcomes included the timed 10-meter walk, nine-hole peg test, and on MRI, T2 and T1 brain lesion loads and brain and spinal cord atrophy.\n The 30- microg dose of interferon beta-1a was well tolerated, but the 60- microg dose caused severe flulike reactions and raised liver enzymes. No treatment effect was seen on the primary endpoint. Subjects on interferon beta-1a 30 microg had a lower rate of accumulation of T2 lesion load than controls (p = 0.025); subjects on 60 microg had a greater rate of ventricular enlargement than controls (p = 0.025).\n This study has demonstrated that interferon beta-1a 30 microg was well tolerated, identified useful outcome measures, but showed no efficacy on the primary outcome measure or on most of the secondary outcome measures.", "Cyclosporine has been effective in patients with steroid-refractory attacks of ulcerative colitis (UC). We investigated the effects of intravenous (IV) cyclosporine as single IV therapy (without glucocorticosteroids) for severe UC and compared these with the response to glucocorticosteroids.\n Patients with a severe attack of UC were randomized to treatment with IV cyclosporine, 4 mg x kg(-1) x day(-1), or with methylprednisolone, 40 mg/day, in a randomized, double-blind, controlled trial. After 8 days, patients who had a response received the same medication orally in combination with azathioprine. Patients were followed up clinically, endoscopically, and by scintigraphy. Renal function was assessed using urinary inulin clearances. Endpoints were clinical improvement, discharge from the hospital, and remission up to 12 months after intravenous therapy.\n Thirty patients were included. After 8 days, 8 of 15 patients (53%) who received methylprednisolone had a response to therapy vs. 9 of 14 (64%) receiving cyclosporine. In nonresponders, 3 of 7 methylprednisolone patients and 1 of 3 cyclosporine patients improved when both treatments were combined. No serious drug-related toxicity was observed with either treatment. At 12 months, 7 of 9 patients (78%) initially controlled with cyclosporine maintained their remission vs. 3 of 8 (37%) initially treated with methylprednisolone. No clinically significant decrease of renal function was observed.\n Cyclosporine monotherapy is an effective and safe alternative to glucocorticosteroids in patients with severe attacks of UC." ]

[ "3317057", "19678813", "2193075", "16279903", "1863024", "19766640", "1885075", "15017515", "20049950" ]

[ "Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.", "Clinical trial: ulcerative colitis maintenance treatment with 5-ASA: a 1-year, randomized multicentre study comparing MMX with Asacol.", "Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation. A double-blind placebo controlled trial.", "Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial.", "Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study.", "Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis.", "Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis.", "The optimal dose of 5-aminosalicylic acid in active ulcerative colitis: a dose-finding study with newly developed mesalamine.", "Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study." ]

[ "We assessed oral 5-aminosalicylic acid (5-ASA) prepared with a pH-sensitive polymer coating in 87 patients with mildly to moderately active ulcerative colitis in a double-blind, placebo-controlled trial. Patients were randomly assigned to receive 5-ASA at a dosage of either 4.8 or 1.6 g per day or placebo for six weeks. The outcome was monitored by flexible proctosigmoidoscopic examinations and physicians' assessments at three-week intervals and by patients' recordings of daily symptoms. Results showed 24 percent complete and 50 percent partial responses in those receiving 4.8 g of 5-ASA per day as compared with 5 percent complete and 13 percent partial responses in those receiving placebo (P less than 0.0001, rank-sum test). At a dosage of 1.6 g per day, the response was twice as good as with placebo, but the difference did not reach statistical significance (P = 0.51). Age, sex, duration of disease, duration of active symptoms, or extent of disease did not affect the clinical outcome. We conclude that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy, at least in the short term, for mildly to moderately active ulcerative colitis.", "5-ASA-MMX (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis.\n To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study.\n In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for >or=1 month prior to the trial, with >or=1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months' treatment.\n In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated.\n Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis.", "Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (less than 20 cm) entered the trial. Thirty-two were treated with 5-ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p less than 0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis.", "Preliminary data have shown that delayed release oral mesalamine (Asacol) dosed at 4.8 g/day provided additional efficacy benefit compared to 1.6 g/day in patients with mildly to moderately active ulcerative colitis. Additionally, Asacol dosed at 2.4 g/day has been proved to be more effective than 1.6 g/day. Whether 4.8 g/day of mesalamine (dosed with an investigational 800 mg tablet) is more effective than Asacol 2.4 g/day (dosed with a 400 mg tablet) in patients with moderately active ulcerative colitis is unknown.\n A randomized, double-blind, controlled trial (ASCEND II) was conducted to evaluate the efficacy of 4.8 g/day of mesalamine in adults with active ulcerative colitis. Three hundred eighty-six patients with mild to moderate ulcerative colitis were randomized for treatment with mesalamine 2.4 g/day (400 mg tablet) or 4.8 g/day (800 mg tablet) for 6 wk. The primary efficacy population was 268 patients with moderately active ulcerative colitis treated with 2.4 g/day (n = 139) or 4.8 g/day (n = 129). The primary endpoint was the proportion of patients in each treatment group that achieved overall improvement (\"treatment success,\" defined as either complete remission or a clinical response to therapy) from baseline at week 6.\n Seventy-two percent of patients receiving 4.8 g/day of mesalamine for moderate ulcerative colitis (89/124 patients) achieved treatment success at week 6, compared with 59% of those who received 2.4 g/day (77/130 patients) (p= 0.036). Both regimens were well tolerated. Adverse events and clinically significant changes in laboratory results were similar in both treatment groups.\n Patients with moderately active ulcerative colitis treated with 4.8 g/day of mesalamine (800 mg tablet) are significantly more likely to achieve overall improvement at 6 wk compared to patients treated with 2.4 g/day.", "To evaluate the efficacy and safety of a pH-sensitive, polymer-coated oral preparation of mesalamine in patients with mildly to moderately active ulcerative colitis.\n A multicenter, double-blind, placebo-controlled randomized trial.\n Five university-based medical centers, one inflammatory bowel disease center, and three private practice sites.\n A total of 158 patients with newly or previously diagnosed active ulcerative colitis.\n A pH-sensitive, polymer-coated oral preparation of mesalamine (5-aminosalicylic acid) was used at 1.6 and 2.4 g/d for 6 weeks.\n Efficacy was measured by scores for stool frequency, rectal bleeding, patient's functional assessment, sigmoidoscopic findings, and physician's global assessment. Stringent criteria for disease activity were established prospectively.\n The analysis of protocol-compliant patients showed a significant improvement at 3 weeks in patients taking 2.4 g/d of mesalamine compared with patients taking placebo (32% versus 9%; P = 0.003). At 6 weeks, both the 1.6 g/d (43%) and 2.4 g/d (49%) doses were significantly superior to placebo (23%) (P = 0.03 and P = 0.003, respectively). In addition, more patients worsened in the placebo group compared with the 2.4 g/d group (50% versus 19%; P = 0.003); however, there was no statistically significant difference in worsening between the 1.6 g/d mesalamine group and the placebo group. The oral mesalamine tablet was well tolerated, and no clinically significant changes were observed in hematologic, hepatic, or renal laboratory profiles.\n Colon-targeted oral mesalamine at 2.4 g/d is effective therapy for mildly to moderately active ulcerative colitis. It is well tolerated and should provide a viable therapeutic alternative to sulfasalazine.", "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.", "5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p less than 0.001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis.", "5-Aminosalicylate is the gold standard for inducing remission in patients with mildly to moderately active ulcerative colitis. The optimal dose is as yet not defined. Despite some recent developments, the ideal formulation for 5-aminosalicylic acid is still awaited. A new pellet preparation was designed combining slow and delayed release properties. Aims of the study were to find the optimal dose and to test efficacy and safety of a new 5-aminosalicylic acid formulation.\n Three hundred twenty-one patients were included in a double-blind multicenter trial. Inclusion criteria were active ulcerative colitis (Clinical Activity Index [CAI] and Endoscopic Index [EI] according to Rachmilewitz, CAI 6-12; EI >/=4). Three different doses of 5-aminosalicylic acid (0.5 g 3 times a day, 1.0 g 3 times a day, and 1.5 g 3 times a day) were studied for 8 weeks.\n Clinical remission rate (CAI </=4) was highest in the 1.0 g 3 times a day group (66 %), 50% in the 0.5 g 3 times a day group, and 55% in the 1.5 g 3 times a day group. Hierarchical testing showed no significance, indicating a lack of dose response across the 3 mesalamine doses. In addition, times to first clinical response were similar: 26.5 days (1.0 g 3 times a day), 27.5 days (0.5 g 3 times a day), and 21.5 days (1.5 g 3 times a day). Endoscopic improvement was better with 1.0 g mesalamine 3 times a day than with 0.5 g 3 times a day, but overall endoscopic and histologic improvement was not different between treatment groups. Baseline activity, duration, and localization of ulcerative colitis did have some influence on the therapeutic activity, but there was no significant interaction with the dose of the study drug. Safety, with special focus on kidney function, was excellent in all 3 groups.\n There is no significant dose response between mesalamine 1.5 g/day, 3.0 g/day, and 4.5 g/day. The optimal dose to induce remission of ulcerative colitis is 0.5 g 5-aminosalicylic acid 3 times a day. Patients failing with this dose may benefit from an increase of the dose up to 1.0 g 3 times a day, but should also be considered for alternative treatment. A newly developed pellet formulation of 5-aminosalicylic acid has promising efficacy and excellent safety.", "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)." ]

[ "1582239", "8093824", "7884017", "12678168", "1681680", "10971979", "7542829", "7041516", "9221965" ]

[ "Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.", "A controlled Nordic multicentre study of zuclopenthixol acetate in oil solution, haloperidol and zuclopenthixol in the treatment of acute psychosis.", "A double-blind controlled study of intramuscular zuclopenthixol acetate and liquid oral haloperidol in the treatment of schizophrenic patients with acute exacerbation.", "Comparative study of the effectiveness of zuclopenthixol acetate and haloperidol in acutely disturbed psychotic patients.", "Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study.", "A double blind comparison of zuclopenthixol acetate with haloperidol in the management of acutely disturbed schizophrenics.", "Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double-blind parallel-group trial.", "A double-blind clinical investigation of cis(Z)-clopenthixol and clopenthixol in chronic schizophrenic patients.", "Clozapine versus placebo in Huntington's disease: a double blind randomised comparative study." ]

[ "A double-blind, multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics, zuclopenthixol and haloperidol. Patients were allocated at random to receive treatment with one or other of the trial drugs for 8 weeks or until discharge. Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks' treatment. Dosage was chosen and adjusted to the individual patient's condition and response. The average daily doses in Week 4 were 33.5 mg and 10.3 mg, respectively. Clinical assessments, including CGI, BPRS and the UKU side-effect scale, were done at baseline, and after 1, 2, 4, 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8. Both treatments caused a significant reduction in scores with no between-group differences. More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action. Zuclopenthixol caused a significantly greater improvement in 'anxious-depression' factor score than haloperidol. The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups. The extrapyramidal symptoms tended to be transient in the zuclopenthixol group, but not in the haloperidol group. The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute, psychotic patients. There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol.", "Zuclopenthixol acetate--a new injectable formulation with a duration of action of 2-3 days--was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed, psychotic patients. The patients were stratified into 3 diagnostic categories: acute psychoses (48 patients), mania (22 patients), and exacerbation of chronic psychoses (73 patients). The patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Mania Rating Scale (BRMAS) (only manic patients) and globally on the Clinical Global Impression (CGI). The study was an open, randomized multicentre trial with a 6-day treatment period. The zuclopenthixol acetate patients received 1-4 doses, the haloperidol patients 1-26 and the zuclopenthixol patients 1-22 doses. The assessments on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories, with no differences between treatments. The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments. All 3 treatments caused a rapid remission of symptoms on the BRMAS. Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments. Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients.", "We carried out a 9-day double-blind clinical trial comparing intramuscular zuclopenthixol acetate with liquid oral haloperidol in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. A parallel-group design was used with stratification by sex. Zuclopenthixol acetate (50 to 150 mg) was given intramuscularly every 3 days, whereas liquid haloperidol (10 to 30 mg daily) was given orally three times a day, with supplementary doses of each medication given under double-blind conditions when needed for agitation. No other sedative drugs, including benzodiazepines, were administered. The mean daily dose was 18.9 mg for haloperidol as compared with a mean dose per 3 days of 117.6 mg for zuclopenthixol. The two treatments were found to be equally efficacious on the Brief Psychiatric Rating Scale and Clinical Global Impression Scale. Both drugs induced similar extrapyramidal side effects. However, more tremors were associated with zuclopenthixol as was a tendency for tardive dyskinesia to be unmasked at the end of the injection interval. Sedation was higher with zuclopenthixol acetate than with haloperidol. Serum creatinine phosphokinase levels were not significantly increased after zuclopenthixol injections. The results of this trial suggest that zuclopenthixol acetate given intramuscularly every second to third day offers an alternative to conventional liquid oral haloperidol in the management of acute schizophrenia.", "To study the effectiveness, frequency of administration and side effects of zuclopenthixol acetate (ZPTA) and haloperidol (HAL) in the treatment of acute psychotic disturbance with aggression.\n Purposive sampling method was employed in a group of psychotic patients with aggression admitted to Songkla Neuropsychiatric Hospital, they were randomly divided into 2 groups: ZPTA group and HAL group. All of the patients were evaluated daily for 7 consecutive days using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale (CGI). Statistical analysis was performed by using the Student t-test and Linear regression.\n There were 70 patients with diagnosis of schizophrenia, mania and acute psychosis. Thirty-eight patients were randomly assigned to the ZPTA group and were given 50-100 mg of the drug, while 32 patients received HAL 5-10 mg. The result showed a significant reduction in BPRS or CGI scores in both groups. Patients treated with ZPTA required less frequent administration than did those on HAL (p < 0.05). There was no statistically significant difference in the reduction in scores between the two groups. Nor was there a statistical difference in reduction of aggression based on BPRS rating. Each group of patients showed a few side effects of mild degree.\n Both ZPTA and HAL were effective in the treatment of acute psychosis with aggression, but frequency of administration was lower in the ZPTA group", "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.", "The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient. Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were randomised to receive either zuclopenthixol acetate or haloperidol. They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and UKU Side Effects Scale. Apart from repeat injections of the same medication, no other anti-psychotic was given for the duration of the study. 50 subjects entered the study of which 44 completed. 23 were given zuclopenthixol acetate and 21 haloperidol. Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating (p < 0.001). There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days (p > 0.05). More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study. Both groups had minimal side effects. Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic.", "A double-blind, randomized, multi-center, parallel-group study was conducted in Finland to compare the efficacy and safety of risperidone with zuclopenthixol in patients with acute exacerbations of schizophrenia or schizophreniform disorder. Ninety-eight patients were randomly assigned to treatment with risperidone (n = 48) or zuclopenthixol (n = 50), in variable doses, for 6 weeks. The mean daily doses of risperidone and zuclopenthixol at the end of the trial were 8 mg and 38 mg respectively. Efficacy was assessed throughout by the Positive and Negative Syndrome Scale for schizophrenia and Clinical Global Impression. Safety assessments included the Extrapyramidal Symptom Rating Scale, UKU Side-Effect Rating Scale, vital signs, body weight and laboratory screening. The results indicate that risperidone is at least as effective as zuclopenthixol for the treatment of acute schizophrenic episodes, with a trend towards greater improvement in the overall severity of symptoms. The onset of action was significantly shorter with risperidone than with zuclopenthixol. Although the general tolerability of the two drugs was comparable, fewer patients experienced extrapyramidal symptoms with risperidone, so that significantly fewer risperidone-treated patients required antiparkinsonian medication.", "The therapeutic effect of the neuroleptic cis(Z)-clopenthixol has been compared with that of clopenthixol in mainly chronic schizophrenic patients in a double-blind 8-week trial. Forty-nine of the 54 patients in the trial received clopenthixol in the pre-trial period. Ratings with CGI and a single side effects form were done at weeks 0, 2, 4, 6, and 8. The registration of therapeutic effect at week 8 indicated a symptomatological status quo in both groups of patients while there was a tendency of slightly less interference by cis(Z)-clopenthixol with patient's functioning than by clopenthixol. The ratio of therapeutically equipotent cis(Z)-clopenthixol/clopenthixol doses was found to be 1:2. It is suggested that long-term treatment with clopenthixol advantageously may be replaced by cis(Z)-clopenthixol.", "To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease.\n Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately.\n Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties.\n Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group." ]

[ "3883876", "12785023", "14725657", "2690721", "7740420", "7029140", "12614412", "3307653", "9163286" ]

[ "Varicose veins: optimum compression following sclerotherapy.", "Foam-sclerotherapy, surgery, sclerotherapy, and combined treatment for varicose veins: a 10-year, prospective, randomized, controlled, trial (VEDICO trial).", "Evaluation of the efficacy of polidocanol in the form of foam compared with liquid form in sclerotherapy of the greater saphenous vein: initial results.", "Varicose veins: optimum compression after surgery and sclerotherapy.", "Mesocaval shunt or repeated sclerotherapy: effects on rebleeding and encephalopathy--a randomized trial.", "A random controlled trial of two forms of compression bandaging in outpatient sclerotherapy of varicose veins.", "Ambulatory phlebectomy versus compression sclerotherapy: results of a randomized controlled trial.", "Shunt surgery versus endoscopic sclerotherapy for long-term treatment of variceal bleeding. Early results of a randomized trial.", "Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial." ]

[ "There is uncertainty regarding the most satisfactory technique of lower limb compression following sclerotherapy for varicose veins. We have compared a standard bandaging technique with a high pressure compression stocking in a randomised trial. Efficacy was judged on the success of injections, complications of the treatment and patient satisfaction. In the stockinged legs 144 of 156 injections were successful, compared with 117 of 147 in the bandaged group (P less than 0.001) (Chi squared). The incidence of superficial thrombophlebitis was also reduced in the stocking group. In addition, the stocking technique costs less in materials than conventional bandaging. We would recommend compression stockings for evaluation in sclerotherapy of varicose veins.", "The study compared, by a prospective, randomized method, 6 treatment options: A: Sclerotherapy; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclerotherapy; F: Surgery (ligation) followed by sclerotherapy. Results were analyzed 10 years after inclusion and initial treatment. Endpoints of the study were variations in ambulatory venous pressure (AVP), refilling time (RT), presence of duplex-reflux, and number of recurrent or new incompetent venous sites. The number of patients, limbs, and treated venous segments were comparable in the 6 treatment groups, also comparable for age and sex distribution. The occurrence of new varicose veins at 5 years varied from 34% for group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins varied from 37% in F to 56% in A. At inclusion AVP was comparable in the different groups. At 10 years the decrease in AVP and the increase in RT (indicating decrease in reflux), was generally comparable in the different groups. Also at 10 years the number of new points of major incompetence was comparable in all treatment groups. These results indicate that, when correctly performed, all treatments may be similarly effective. \"Standard,\" low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain, in selected subjects, results comparable to surgery.", "Foamed sclerosing agents have been used with enthusiasm by phlebologists for more than 5 decades. Any type of varicose veins can and has been treated with this technique. Numerous publications have stressed the advantages of foamed sclerosing agents on the basis of empiric and experimental criteria and have described various individual techniques to prepare foams. Until now, however, no comparative study for the treatment of large varicose veins with foam or liquid exists.\n The purpose of this first randomized, prospective, multicenter trial was to study the elimination of reflux, the rate of recanalization, and possible side effects of foam sclerotherapy (FS) compared with conventional liquid sclerotherapy for the greater saphenous vein (GSV).\n Eighty-eight patients were randomized into two groups: One group was treated with sclerosing foam (45 patients) and the other with sclerosing liquid (43 cases). Sclerotherapy was performed with direct puncture of the vessel under duplex guidance. The reference sclerosing agent was polidocanol in a 3% solution. The foam was prepared using the Double Syringe System (DSS) method. Only one injection of 2.0 or 2.5 mL liquid or foam was allowed, depending on the diameter of the GSV. Results were assessed according to the protocol.\n Follow-up after 3 weeks showed 84% elimination of reflux in the GSV with DSS foam versus 40% with liquid sclerosant (P < 0.01). At 6 months, six recanalizations were found in the liquid group versus two in the foam group. After 1 year, no additional recanalization was observed with either foam or liquid. Longer term studies are underway. Side effects did not differ between both groups.\n The efficacy of sclerosing foam (DSS) compared with sclerosing liquid in therapy of the GSV is superior, a finding that had already gained empirical recognition but for which there has not been any clinical evidence to date.", "Graduated compression stockings are used in both surgical and non-surgical treatment of varicose veins. In a trial of high versus low compression stockings (40 mmHg vs 15 mmHg at ankle) after varicose vein surgery, both were equally effective in controlling bruising and thrombophlebitis, but low compression stockings proved to be more comfortable. In a further trial after sclerotherapy, high compression stockings alone produced comparable results to Elastocrepe bandages with stockings. It is concluded that after varicose vein surgery low compression stockings provide adequate support for the leg and that after sclerotherapy, bandaging is not required if a high compression stocking is used.", "Sclerotherapy is usually effective in controlling acutely bleeding esophageal varices. It may not be as effective as shunt surgery for prevention of rebleeding; therefore we undertook a prospective study comparing interposition mesocaval shunt (MCS) and repeated sclerotherapy.\n Forty-five patients (mean age, 52.6 +/- 9.8 years) with variceal bleeding were randomized after emergency endoscopic sclerotherapy either to repeat variceal obliteration followed by regular check endoscopy (n = 21) or to elective interposition mesocaval shunting by use of 14 mm polytetrafluoroethylene graft (n = 24). There was an equal distribution of Child's classes in the two groups.\n In the sclerotherapy group 12 patients had recurrent hemorrhages causing five deaths compared with the shunt group, in which four patients had postoperative bleeding but without associated death. No difference was noted in the incidence of encephalopathy despite the development of total shunting 1 year after MCS. The median hospital stay was similar; 34.5 days (MCS) and 33 days (sclerotherapy). The number of intensive care unit days was also similar in the two groups. No difference was noted in survival in patients with Child's A and Child's B disease in the treatment groups. In patients with Child's C cirrhosis there was a statistically significant longer survival in patients undergoing MCS compared with patients undergoing sclerotherapy.\n The results of the study show that the rate of rebleeding is significantly higher after sclerotherapy than after mesocaval shunting. In patients with Child's C cirrhosis MCS may be an alternative to sclerotherapy for the prevention of rebleeding from esophageal varices in patients not suitable for transplantation.", "nan", "Although no randomized controlled trial has assessed the effects of either compression sclerotherapy or ambulatory phlebectomy, both techniques are used to treat varicose veins worldwide. We performed a randomized controlled trial to compare recurrence rates of varicose veins and complications after compression sclerotherapy and ambulatory phlebectomy.\n From September 1996 to October 1998, we randomly allocated 49 legs to compression sclerotherapy and 49 legs to ambulatory phlebectomy. Our primary outcome parameters were as follows: recurrence rates at 1 and 2 years and complications related to therapy. Eighty-two patients were included, of whom 16 were included with both of their legs. The number of treated legs was therefore 98, but two patients were lost to follow-up.\n One year recurrence amounted to 1 out of 48 for phlebectomy and 12 out of 48 for compression sclerotherapy (P<0.001); at 2 years, six additional recurrences were found, but then solely for compression sclerotherapy (P<0.001). Significant differences in complications occurring more in phlebectomy than in compression sclerotherapy therapy were blisters, teleangiectatic matting, scar formation, and bruising from bandaging.\n Our results show that ambulatory phlebectomy is an effective therapy for varicose veins of the leg. Recurrence rates are significantly lower than for compression sclerotherapy therapy. If varicose veins persist 4 weeks after compression sclerotherapy, it can be argued that to reduce the risk of future recurrence ambulatory phlebectomy should be considered as the better treatment option.", "In September 1982, a prospective randomized trial comparing shunt surgery and endoscopic sclerotherapy for the elective management of variceal hemorrhage in patients with cirrhosis was initiated. Twenty-seven patients have received shunts (distal splenorenal = 23, nonselective = 4) and 30 patients have had chronic sclerotherapy. Eighty-six per cent of patients had alcoholic cirrhosis and 33% were Child's class C. After a mean follow-up of 25 months, 19% of shunt and 57% of sclerotherapy patients have had rebleeding (p = 0.003). Kaplan-Meier survival analysis reveals similar 2-year survival rates for shunt (65%) and sclerotherapy (61%) groups. Only two of 10 sclerotherapy failures have been salvaged by surgery. Posttherapy quantitative hepatic function, frequency of encephalopathy, and cumulative medical costs were similar for both groups. Hepatic portal perfusion and portal pressure at 1 year were better maintained by sclerotherapy than by distal splenorenal shunt. In conclusion, endoscopic sclerotherapy and shunt surgery provide similar results with respect to survival, hepatic function, frequency of encephalopathy, and costs. Sclerotherapy is an acceptable, but not superior, alternative to shunt surgery for treatment of variceal hemorrhage.", "Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency.\n To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices.\n Randomized, controlled clinical trial.\n Three teaching hospitals.\n 49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS.\n Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein.\n Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs.\n Mean follow-up (+/-SE) was 567 +/- 104 days in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]).\n In obliterating varices and reducing rebleeding events from esophageal varies, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant." ]

[ "15017504", "9691103", "8533995", "19766640", "17241860", "1863024", "19375519", "20049949", "9382054" ]

[ "Budesonide versus mesalamine for maintaining remission in patients refusing other immunomodulators for steroid-dependent Crohn's disease.", "A comparison of budesonide and mesalamine for active Crohn's disease. International Budesonide-Mesalamine Study Group.", "An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis. A randomized, placebo-controlled trial. The Mesalamine Study Group.", "Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis.", "Once-daily, high-concentration MMX mesalamine in active ulcerative colitis.", "Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study.", "Mesalamine once daily is more effective than twice daily in patients with quiescent ulcerative colitis.", "Direct comparison of two different mesalamine formulations for the maintenance of remission in patients with ulcerative colitis: a double-blind, randomized study.", "A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis." ]

[ "To compare the efficacy of controlled-release budesonide capsules with that of mesalamine for maintaining remission and improving quality of life (QOL) in patients with steroid-dependent Crohn's disease.\n Fifty-seven patients (25 men; mean age, 32 +/- 10.1 yr) with quiescent steroid-dependent Crohn's ileitis, ileocolitis, or colitis (Crohn's disease activity index <150) entered a prospective, investigator-blind trial. Patients were eligible for treatment with azathioprine but had not consented or had developed side effects. Patients were randomized to receive budesonide 6 mg/day (n = 29) or mesalamine 1 g 3 times/day (n = 28). Follow-up assessments were made every 2 months for up to 1 year or until relapse. At each visit, quality of life (QOL) was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ).\n There were no significant differences in baseline clinical characteristics between the study groups. The 1-year relapse rate was significantly lower in the budesonide group than in the mesalamine group (55% vs. 82%; 95% confidence interval, 12.4%-41%; P = 0.045). Patients assigned to budesonide also remained in remission longer (241 +/- 114 days vs. 147 +/- 117 days; 95% confidence interval, 32.7-155.3 days; P = 0.003). Compared with mesalamine, budesonide treatment also was associated with a better QOL throughout the study (mean total IBDQ scores 165 +/- 36 vs. 182 +/- 28, respectively; 95% confidence interval, -0.4 to 34.4, P = 0.0001). This advantage was confirmed in patients' self-assessed QOL scores.\n Over a 1-year period, controlled-release budesonide was significantly more effective than mesalamine for maintaining remission and improving the QOL of patients with steroid-dependent Crohn's disease.", "Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both.\n In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index.\n In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02).\n In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.", "To compare the safety and efficacy of a pH-sensitive, polymer-coated oral formulation of mesalamine (Asacol, Procter & Gamble Pharmaceuticals, Cincinnati, Ohio) with those of placebo in maintaining remission in patients with ulcerative colitis.\n Multicenter, double-blind, placebo-controlled, randomized clinical trial.\n Eight private practices, five university-based medical centers, and four hospitals or clinics.\n 264 patients with ulcerative colitis that had been maintained in remission for at least 1 month while the patients were receiving stable doses of sulfasalazine or any oral mesalamine product.\n Coated mesalamine at oral dosages of 0.8 g/d or 1.6 g/d or matching placebo for 6 months.\n Treatment success, defined as maintenance of remission after 6 months, and treatment failure, defined as relapse during the study (as indicated by proctosigmoidoscopy at 1, 3, or 6 months of treatment) or withdrawal due to adverse events. Safety was assessed on the basis of laboratory analyses and patient- and investigator-noted adverse events.\n 189 patients were compliant with the protocol for 6 months or stopped receiving therapy because of relapse or adverse events. Of these 189 patients, 25 of the 63 patients (39.7%) in the placebo group had treatment success compared with 40 of the 68 patients (58.8% [95% CI, 46.4% to 71.3%]) in the group receiving mesalamine, 0.8 g/d (P = 0.036) and 38 of the 58 patients (65.5% [CI, 52.4% to 78.6%]) in the group receiving mesalamine, 1.6 g/d (P = 0.006). In the intention-to-treat analysis of all patients, 42 of the 87 patients (48.3%) in the placebo group had treatment success compared with 57 of the 90 patients (63.3% [CI, 52.8% to 73.8%]) in the group receiving mesalamine, 0.8 g/d (P = 0.050) and 61 of the 87 patients (70.1% [CI, 59.9% to 80.3%]) in the group receiving mesalamine, 1.6 g/d (P = 0.005). Age, sex, and race were not found to predict treatment success or failure. The mesalamine tablet was well tolerated, and no clinically significant changes were seen in hematologic, hepatic, or renal laboratory profiles.\n Coated mesalamine at oral dosages of 0.8 g/d and 1.6 g/d is safe and effective in maintaining remission in patients with quiescent ulcerative colitis.", "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.", "SPD476 (LIALDA in the US; MEZAVANT in the EU; otherwise known as MMX mesalamine; Shire Pharmaceuticals Inc., Wayne, PA, under license from Giuliani SpA, Milan, Italy) is a novel, once-daily, high-strength (1.2 g/tablet) formulation of mesalamine, utilizing MMX Multi Matrix System (MMX) technology designed to deliver the active drug throughout the colon. We performed a double-blind, multicenter study, comparing MMX mesalamine vs placebo for the treatment of active ulcerative colitis. A delayed-release oral mesalamine (ASACOL; Procter & Gamble, Cincinnati, OH) reference arm was included.\n Three hundred forty-three patients with active, mild-to-moderate ulcerative colitis received MMX mesalamine 2.4 g/day or 4.8 g/day given once daily, ASACOL 2.4 g/day given in 3 divided doses, or placebo for 8 weeks. The primary end point was the proportion of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index of < or =1 with rectal bleeding and stool frequency scores of 0, no mucosal friability, and a > or =1-point reduction in sigmoidoscopy score from baseline).\n A significantly greater proportion of patients receiving MMX mesalamine 2.4 g/day given once daily (40.5%; P = .01) and 4.8 g/day given once daily (41.2%; P = .007) achieved clinical and endoscopic remission at week 8, vs placebo (22.1%). The clinical and endoscopic remission rate for ASACOL (32.6%; P = .124) was not significantly superior to placebo. All active treatments were well-tolerated.\n Once-daily MMX mesalamine was efficacious and well-tolerated for the induction of clinical and endoscopic remission. MMX mesalamine offers effective and convenient mesalamine therapy, potentially improving treatment compliance.", "To evaluate the efficacy and safety of a pH-sensitive, polymer-coated oral preparation of mesalamine in patients with mildly to moderately active ulcerative colitis.\n A multicenter, double-blind, placebo-controlled randomized trial.\n Five university-based medical centers, one inflammatory bowel disease center, and three private practice sites.\n A total of 158 patients with newly or previously diagnosed active ulcerative colitis.\n A pH-sensitive, polymer-coated oral preparation of mesalamine (5-aminosalicylic acid) was used at 1.6 and 2.4 g/d for 6 weeks.\n Efficacy was measured by scores for stool frequency, rectal bleeding, patient's functional assessment, sigmoidoscopic findings, and physician's global assessment. Stringent criteria for disease activity were established prospectively.\n The analysis of protocol-compliant patients showed a significant improvement at 3 weeks in patients taking 2.4 g/d of mesalamine compared with patients taking placebo (32% versus 9%; P = 0.003). At 6 weeks, both the 1.6 g/d (43%) and 2.4 g/d (49%) doses were significantly superior to placebo (23%) (P = 0.03 and P = 0.003, respectively). In addition, more patients worsened in the placebo group compared with the 2.4 g/d group (50% versus 19%; P = 0.003); however, there was no statistically significant difference in worsening between the 1.6 g/d mesalamine group and the placebo group. The oral mesalamine tablet was well tolerated, and no clinically significant changes were observed in hematologic, hepatic, or renal laboratory profiles.\n Colon-targeted oral mesalamine at 2.4 g/d is effective therapy for mildly to moderately active ulcerative colitis. It is well tolerated and should provide a viable therapeutic alternative to sulfasalazine.", "Oral mesalamine (5-aminosalicylate) is the current standard of care for mild-to-moderate ulcerative colitis. We investigated the efficacy and safety of once daily administration of prolonged-release mesalamine granules in maintenance of remission in patients with quiescent ulcerative colitis, compared with the well established twice daily dosing regimen.\n In this multicenter, randomized, single blind, noninferiority trial, 362 patients with quiescent ulcerative colitis were randomly assigned (1:1) to groups that were given oral mesalamine 2 g, once daily, or 1 g, twice daily, for 12 months. The primary objective was to compare remission rates at 1 year, based on the ulcerative colitis disease activity index score, using Kaplan-Meier methodology.\n At 1 year, 70.9% of the group given 2 g mesalamine once daily remained in remission vs 58.9% of the group given 1 g mesalamine twice daily; this difference was statistically significant (P = .024), indicating the increased efficacy of once daily, compared with twice daily, dosing. Self-reported adherence to therapy, measured by visual analog scale score after 4, 8, and 12 months, was significantly greater in the group given 2 g mesalamine once daily, compared with twice daily, at all but 1 study visit (P < .05). Compliance measured by medication taken was not significantly different between the groups. The difference between the 2 groups in overall incidence of adverse events was not statistically significant (P = .23).\n Patients with ulcerative colitis given prolonged-release oral mesalamine 2 g once daily had better remission rates, acceptability, and self-reported adherence to therapy compared with patients given oral mesalamine 1 g twice daily.", "Mesalamine has been used as the first-line medication for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two different mesalamine formulations in the maintenance of remission in patients with UC.\n In a multicenter, double-blind, randomized study, 131 patients with quiescent UC were assigned to two groups: 65 to receive a pH-dependent release formulation of mesalamine at 2.4 g/day (pH-2.4 g) and 66 to receive a time-dependent release formulation of mesalamine at 2.25 g/day (Time-2.25 g). Both formulations were administered three times daily for 48 weeks. The primary endpoint was the proportion of patients without bloody stools.\n In the full analysis set (n = 130), the proportion of patients without bloody stools was 76.9% in the pH-2.4 g and 69.2% in the Time-2.25 g, demonstrating the noninferiority of pH-2.4 g to Time-2.25 g. No statistically significant difference in time to bloody stools was found between the two formulations (P = 0.27, log-rank test), but the time to bloody stools tended to be longer in pH-2.4 g compared to Time-2.25 g, and a similar trend was observed with regard to the time to relapse. No differences were observed between the safety profiles of the two formulations.\n The pH- and time-dependent release of mesalamine formulations were similarly safe and effective. Interestingly, the remission phase tended to be longer in the group that received the pH-dependent formulation compared to the group that received the time-dependent formulation (UMIN Clinical Trials Registry, no. C000000289).", "The aim of this study was to compare the efficacy of mesalamine rectal suspension enema (Rowasa) alone, oral mesalamine tablets (Asacol) alone, and the combination of mesalamine enema and mesalamine tablets in patients with active mild-to-moderate distal ulcerative colitis.\n Sixty outpatients with ulcerative colitis at least 5 cm above the anal verge and not more than 50 cm, inclusive, and a total disease activity index (DAI) score between 4 and 10, inclusive, were randomized to either mesalamine rectal enema (n = 18) once nightly, oral mesalamine 2.4 g/day (n = 22), or a combination of both treatments (n = 20). Placebo capsules and enemas were used to maintain a blind procedure. Total DAI scores and abbreviated DAI scores were evaluated at wk 3 and 6, and wk 1 and 2, respectively. Patients recorded the amount of blood in stools, urgency, straining at stools, and abdominal pain in daily diaries. Physicians and patients rated overall improvement at each visit.\n At wk 6, combination therapy produced a greater improvement (-5.2) in total DAI scores than did either mesalamine enema (-4.4) or mesalamine tablet (-3.9) therapy alone; similar treatment differences were observed at wk 3. Compared with patients given mesalamine enemas or mesalamine tablets, combination-therapy patients reported an absence of blood in stools significantly sooner and, at all visits, the combination therapy group had the highest percentage of patients who reported no blood in their stools. Physicians' and patients' ratings of improvement indicated that combination therapy significantly improved disease status, compared with mesalamine tablet therapy alone. All treatments were well tolerated.\n The combination of oral and rectal mesalamine therapy was well tolerated and produced earlier and more complete relief of rectal bleeding than oral or rectal therapy alone." ]

[ "18569754", "3941301", "3812046", "16766441", "1873454", "3716918", "3369332", "17074945", "19524389" ]

[ "Hypnosis for smoking cessation: a randomized trial.", "A randomized controlled trial of hypnotherapy for smoking cessation.", "Treatment effectiveness of hypnosis and behaviour therapy in smoking cessation: a methodological refinement.", "Intensive hypnotherapy for smoking cessation: a prospective study.", "A randomized trial of smoking cessation interventions in general practice in Italy.", "Hypnosis and behavioral treatment in a worksite smoking cessation program.", "Use of single session hypnosis for smoking cessation.", "A randomized controlled trial of a smoking cessation intervention among people with a psychotic disorder.", "Impact of a brief motivational smoking cessation intervention the Get PHIT randomized controlled trial." ]

[ "The purpose of this study was to determine whether hypnosis would be more effective in helping smokers quit than standard behavioral counseling when both interventions are combined with nicotine patches (NP). A total of 286 current smokers were enrolled in a randomized controlled smoking cessation trial at the San Francisco Veterans Affairs Medical Center. Participants in both treatment conditions were seen for two 60-min sessions, and received three follow-up phone calls and 2 months of NP. At 6 months, 29% of the hypnosis group reported 7-day point-prevalence abstinence compared with 23% of the behavioral counseling group (relative risk [RR] = 1.27; 95% confidence interval, CI 0.84-1.92). Based on biochemical or proxy confirmation, 26% of the participants in the hypnosis group were abstinent at 6 months compared with 18% of the behavioral group (RR = 1.44; 95% CI 0.91-2.30). At 12 months, the self-reported 7-day point-prevalence quit rate was 24% for the hypnosis group and 16% for the behavioral group (RR = 1.47; 95% CI 0.90-2.40). Based on biochemical or proxy confirmation, 20% of the participants in the hypnosis group were abstinent at 12 months compared with 14% of the behavioral group (RR = 1.40; 95% CI 0.81-2.42). Among participants with a history of depression, hypnosis yielded significantly higher validated point-prevalence quit rates at 6 and 12 months than standard treatment. It was concluded that hypnosis combined with NP compares favorably with standard behavioral counseling in generating long-term quit rates.", "A randomized controlled study in a family practice setting was conducted on the use of hypnosis in helping people quit smoking. In the hypnosis group 21 percent of patients quit smoking by the three month follow-up compared with 6 percent in the control group. By six months there were no significant differences between the two groups, and at one year 22 percent in the hypnosis group and 20 percent in the control group had quit. The only significant predictor of success with quitting was having a college education.", "Studies in smoking cessation have generally failed to adequately control for active treatment effects and have assumed that measures of smoking behaviour (i.e., estimated smoking rate, self-monitoring and chemical analysis) are equally reliable measures. Sixty smokers were randomly assigned to one of four different smoking cessation treatment groups: hypnosis, focussed smoking, attention placebo and a waiting list control. Subjects were asked to estimate and monitor their own smoking behaviour. Blood samples were also taken for thiocyanate analysis before treatment. Smoking rates were similarly measured directly, at 3 months and 6 months after treatment. The results indicate that the three measures of smoking behaviour were all highly correlated. No significant differences were found between treatments, directly after treatment or at the 3- and 6-month follow-ups. These results suggest that active treatment effects may not be responsible for behavioural change in a smoking cessation program. The implications of these findings are discussed.", "This study reports on a prospective pilot trial of intensive hypnotherapy for smoking cessation. The hypnotherapy involved multiple individual sessions (8 visits) over approximately 2 months, individualization of hypnotic suggestions, and a supportive therapeutic relationship. Twenty subjects were randomly assigned to either an intensive hypnotherapy condition or to a wait-list control condition. The target quitting date was 1 week after beginning treatment. Patients were evaluated for smoking cessation at the end of treatment and at Weeks 12 and 26. Self-reported abstinence was confirmed by a carbon-monoxide concentration in expired air of 8 ppm or less. The rates of point prevalence smoking cessation, as confirmed by carbon-monoxide measurements for the intensive hypnotherapy group, was 40% at the end of treatment; 60% at 12 weeks, and 40% at 26 weeks (p < .05).", "The purpose of this study was to examine the effectiveness of different practice-based approaches to assist patients of primary care physicians to quit smoking and sustain cessation. Forty-four nonsmoking general practitioners volunteered for the study. After a period of training, they randomized 923 smoking clients, unselected for motivation toward quitting, to four different intervention groups: (i) minimal intervention, consisting of one single counselling session and a brief handout on quitting techniques; (ii) repeated counselling including reinforcing sessions at Months 1, 3, 6, and 9; (iii) repeated counselling and use of nicotine gum; and (iv) repeated counselling and spirometry. Biochemically validated smoking status was assessed at six and 12 months after recruitment. The proportion of verified quitters at 12 months was 4.8 percent among subjects randomized to the minimal intervention group, compared to 5.5 percent, 7.5 percent, and 6.5 percent among those randomized to the three repeated-counselling groups. In no treatment group was the outcome significantly different from that for one-time counselling at the (P less than 0.05) level. Lack of power, contamination, and low attendance at reinforcing sessions should be taken into account in interpreting the results.", "In the initial study, 48 subjects of the total (N = 63) ultimately used, were assigned to one of three treatments: four hypnotic sessions with a booster, two hypnotic sessions, or two hypnotic and two behavioral sessions with a booster. A follow-up group was later recruited composed of 15 subjects who received four hypnotic sessions and a booster session with less time between sessions. The results indicated no difference in smoking cessation 6 months after treatment regardless of the frequency, length between sessions, or addition of behavioral methods. Successful subjects were more educated, less able to utilize their imagination, and had fewer smokers at home.", "Twenty of sixty volunteers for smoking cessation were assigned to single-session hypnosis, 20 to a placebo control condition, and 20 to a no-treatment control condition. The single-session hypnosis group smoked significantly less cigarettes and were significantly more abstinent than a placebo control group and a no treatment control group at posttest, and 4-week, 12-week, 24-week and 48-week follow-ups.", "Despite extremely high rates of smoking among individuals with psychotic disorders and the associated financial and health costs, few studies have investigated the efficacy of smoking cessation interventions among this group. The purpose of this study was to compare an integrated psychological and nicotine replacement therapy intervention for people with a psychotic disorder with routine care alone.\n The authors recruited 298 regular smokers with a psychotic disorder residing in the community and randomly assigned them to a routine care comparison condition (N=151) or an eight-session, individually administered smoking cessation intervention (N=147), which consisted of nicotine replacement therapy, motivational interviewing, and cognitive behavior therapy. Outcome variables included continuous and point-prevalence abstinence rates, smoking reduction status, and changes in symptoms and functioning.\n While there were no overall differences between the treatment group and comparison group in abstinence rates, a significantly higher proportion of smokers who completed all treatment sessions stopped smoking at each of the follow-up occasions (point-prevalence rates: 3 months, 30.0% versus 6.0%; 6 months, 18.6% versus 4.0%; and 12 months, 18.6% versus 6.6%). Smokers who completed all treatment sessions were also more likely to have achieved continuous abstinence at 3 months (21.4% versus 4.0%). There was a strong dose-response relationship between treatment session attendance and smoking reduction status, with one-half of those who completed the intervention program achieving a 50% or greater reduction in daily cigarette consumption across the follow-ups, relative to less than one-fifth of the comparison subjects. There was no evidence of any associated deterioration in symptoms or functioning.\n These findings demonstrate the utility of a nicotine replacement therapy plus motivational interviewing/cognitive behavior therapy smoking cessation intervention among individuals with a psychotic disorder. Further development of more efficacious interventions is required for those who do not respond to existing interventions.", "Few studies have rigorously evaluated whether providing biologically based health-risk feedback is more effective than standard interventions in increasing smokers' motivation to quit and their long-term abstinence.\n An RCT was conducted from 2005 to 2008. Data were analyzed in 2008.\n Smokers (N=536) were recruited from the community, regardless of their interest in quitting smoking.\n Smokers either received brief ( approximately 20 minutes), personally tailored counseling sessions based on their lung functioning, carbon monoxide (CO) exposure, and smoking-related health conditions, or they received generic smoking-risk information and personalized counseling about their diet, BMI, and physical activity. All were advised to quit smoking and were offered access to a free phone-counseling program.\n Treatment utilization and abstinence at 6 and 12 months post-intervention.\n Participants who received the experimental treatment demonstrated no greater motivation to quit, use of treatment services, or abstinence compared to controls at either follow-up assessment. In fact, controls reported greater motivation to quit at 12 months (M 3.42 vs 3.20, p=0.03), greater use of pharmacotherapy at 6 months (37.8% vs 28.0%, p=0.02), and greater 30-day point prevalent abstinence at 6 months, after controlling for relevant covariates (10.8% vs 6.4%, adjusted p=0.04).\n The present study found no support for adding a personalized health-risk assessment emphasizing lung health and CO exposure to generic cessation advice and counseling for community-based smokers not otherwise seeking treatment.\n NCT00169260." ]

[ "1670783", "17710485", "11340701", "9648698", "12134249", "9773910", "2267922", "18005909", "11486442" ]

[ "Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial.", "Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.", "Intranasal beclomethasone dipropionate in the treatment of common cold.", "The common cold: effects of intranasal fluticasone propionate treatment.", "Combined antiviral-antimediator treatment for the common cold.", "Efficacy of corticosteroids in acute bronchiolitis: short-term and long-term follow-up.", "Placebo controlled trial of systemic corticosteroids in acute childhood asthma.", "Efficacy of a pelargonium sidoides preparation in patients with the common cold: a randomized, double blind, placebo-controlled clinical trial.", "Topical corticosteroids in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial using fluticasone propionate aqueous nasal spray." ]

[ "We tested the hypothesis that antihistamine-decongestant combinations cause no clinically significant relief of the symptoms of upper respiratory tract infections in young children by randomly assigning 96 children to one of three treatment groups: antihistamine-decongestant, placebo, and no treatment. There were no differences among the three study groups in the proportion of children considered \"better\" overall by the parent 48 hours after the initial assessment (drug, 67%; placebo, 71%; no treatment, 57%; p = 0.53). There were no differences among groups in individual or composite symptom score changes. Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms. In the proportion of parents believing that their child needed medicine, there was no difference between those who consented to participate and those who refused. Parents who wanted medicine at the initial visit reported more improvement at follow-up, regardless of whether the child received drug, placebo, or no treatment. We conclude that there is no clinically significant improvement in symptoms of upper respiratory tract infection, including no significant placebo effect, in young children for whom an antihistamine-decongestant is prescribed.", "Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.\n The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.\n An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.\n Thirty-one adult CAP patients who required hospitalization were enrolled.\n Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.\n In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.", "Sinusitis is usually considered a complication of viral rhinitis. Virus infections in the upper respiratory tract lead to mucosal swelling, which may obstruct paranasal sinus outflow, resulting in infection in the paranasal sinuses. Topical nasal steroids have been found beneficial in a variety of acute and chronic nasal conditions including allergic and nonallergic rhinitis and chronic rhinosinusitis. The purpose of this study was to examine whether the intranasal inhalation powder beclomethasone dipropionate (BDP) 400 micrograms/day treatment has a beneficial or harmful effect on symptoms and signs of common cold, and whether or not it can prevent common cold complications. A total of 54 patients were randomized, 26 into the placebo-group and 28 into the BDP group. During the 14-day follow-up, there were on an average 10.3 symptomatic days in the placebo group and 10.7 days in the BDP group (p = 0.72). The use of intranasal BDP in the treatment of common cold neither reduced symptoms caused by inflammation nor did it shorten the recovery time. On the other hand, because BDP does not increase the risk of complications or significantly prolong the recovery during the common cold, there is no need to discontinue its use in the patients with allergic rhinitis or nasal polyposis.", "A double-blind, randomized, placebo-controlled trial was conducted to study the effect of the intranasal corticosteroid, fluticasone propionate (FP), in the naturally occurring common cold.\n One hundred ninety-nine young adults received high-dose FP (200 microg four times daily) or placebo beginning 24 to 48 hours after onset of the common cold for 6 days. All symptoms were recorded on diary cards on days 1 to 20, and clinical examinations were carried out on days 1, 7, and 21. Nasopharyngeal aspirates were collected on days 1 and 7 for detection of rhinoviruses (found in 105 subjects) and Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis (found in 52 subjects) in the nasopharynx.\n In general, FP treatment had no clinically recognizable effects on the symptoms of the common cold, although it significantly reduced nasal congestion and cough on some study days. After treatment, rhinoviruses were cultured more often in the FP treatment group (37% vs 14%, p < 0.001), but this had no effect on the symptoms of common cold. FP treatment produced no changes in the colonization of pathogenic bacteria in the nasopharynx. Some symptoms of common cold were significantly more severe during days 1 to 10 (p < 0.05) in subjects found to have positive cultures for S. pneumoniae, H. influenzae, or M. catarrhalis in the nasopharynx on day 1 (n = 33).\n FP treatment does not have any marked effects on the symptoms of the common cold. FP treatment induced prolonged shedding of viable rhinoviruses. Some symptoms of the common cold were significantly more severe in subjects with pathogenic bacteria in the nasopharynx.", "A randomized, controlled, double-masked clinical trial was conducted with a combination antiviral-antimediator treatment for experimental rhinovirus colds. In all, 150 healthy men and women (aged 18-51 years) were randomly assigned to 1 of 3 groups: intranasal interferon (IFN)-alpha2b (6 x 10(6) U every 12 h x 3) plus oral chlorpheniramine (12 mg extended release) and ibuprofen (400 mg) every 12 h for 4.5 days (n=59 subjects); intranasal placebo plus oral chlorpheniramine and ibuprofen (n=61 subjects); or intranasal and oral placebos (n=30 subjects). Treatment was started 24 h after intranasal viral challenge. During the 4.5 days of treatment with IFN-alpha2b, chlorpheniramine, and ibuprofen, the daily mean total symptom score was reduced by 33%-73%, compared with placebo. Treatment reduced the severity of rhinorrhea, sneezing, nasal obstruction, sore throat, cough, and headache and reduced nasal mucus production, nasal tissue use, and virus concentrations in nasal secretions. IFN-alpha2b added to the effectiveness of chlorpheniramine and ibuprofen and was well tolerated.", "Corticosteroids continue to be used by many physicians to treat infants with bronchiolitis. The aim of this study was to examine the short-term and long-term efficacy of oral corticosteroid therapy when added to beta2-agonists in infants with mild to moderate bronchiolitis (defined as the first episode of wheezing associated with low grade fever, rhinitis, tachypnea, and increased respiratory effort in a previously healthy infant during the winter months). Infants with mild to moderate bronchiolitis, were randomly assigned to receive either oral prednisone (2 mg/kg/day) or placebo for 3 days. All patients received nebulized albuterol q.i.d. during this period. Upon admission and after 3 days of therapy, a clinical score was assigned based on respiratory rate, use of accessory muscle, and the presence of wheeze. Oxygen saturation (SaO2) was also measured. On day 7, we inquired as to the well-being of each child. Two years later, the development of chronic respiratory symptoms was assessed. Thirty-eight infants were enrolled in the study; 20 received prednisone and 18 received placebo. Both groups were similar in terms of age, duration of illness prior to enrollment, pretrial medication use, clinical severity of bronchiolitis, history of atopy, and family history of atopy. After 3 and 7 days of treatment, both groups showed similar clinical improvement and there were no statistically significant differences between the two groups in the clinical score or in the SaO2. No major side effects were observed. Two years later, 32% of the infants continued to suffer from chronic respiratory symptoms, with a similar prevalence in both groups. We conclude that a 3-day course of oral corticosteroids is of no benefit to infants with mild to moderate bronchiolitis who are also treated with an inhaled beta2-agonist.", "In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p less than 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p less than 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze-free when they left hospital compared with 3 in the placebo group, p less than 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma.", "The common cold is a viral infection with symptoms such as sneezing, sore throat, and running nose. It is one of the most prevalent illnesses in the world, and although commonly caused by rhinoviruses, antibiotics are often prescribed unnecessarily. Therefore, it is of utmost importance to evaluate alternative treatments such as herbal medications, whose efficacy and safety is proven by pharmacological and clinical studies.\n The aim of the present study was to evaluate the efficacy of a liquid herbal drug preparation from the roots of Pelargonium sidoides compared with placebo in adult patients with the common cold.\n The study was designed as a multicenter, prospective, randomized, double blind, parallel group, placebo-controlled phase III clinical trial with an adaptive group-sequential design.\n The study took place in eight outpatient departments affiliated with hospitals.\n One hundred three male and female adult patients with at least two major and one minor or with one major and three minor cold symptoms (maximum symptom score of 40 points), present for 24 to 48 hours, and who gave provision of informed consent were randomized to receive either 30 drops (1.5 mL) of the liquid herbal drug preparation EPs or placebo three times a day.\n Patients received randomized treatment for a maximum period of 10 days.\n The primary outcome criterion was the sum of symptom intensity differences (SSID) of the cold intensity score (CIS) from day one to day five. The CIS consists of the following 10 cold symptoms: nasal drainage, sore throat, nasal congestion, sneezing, scratchy throat, hoarseness, cough, headache, muscle aches, and fever.\n From baseline to day five, the mean SSID improved by 14.6 +/- 5.3 points in the EPs group compared with 7.6 +/- 7.5 points in the placebo group. This difference was statistically significant (P < .0001). The mean CIS decreased by 10.4 +/- 3.0 points and 5.6 +/- 4.3 points in EPs and placebo-treated patients, respectively. After 10 days, 78.8% versus 31.4% in the EPs versus placebo group were clinically cured (CIS equals zero points or complete resolution of all but a maximum of one cold symptom; P < .0001). The mean duration of inability to work was significantly lower in the EPs treatment group (6.9 +/- 1.8 days) than in the placebo group (8.2 +/- 2.1 days; P = .0003). Treatment outcome (rates of complete recovery or major improvement from disease [integrative medicine outcomes scale]) was assessed better in the EPs treatment group than in the placebo group by both the investigator and the patient on day five (P < .0001). Adverse events occurred in three of 103 patients (2.9%), with two of 52 (3.8%) and one of 51 (2.0%) patients in the EPs and placebo group, respectively. All adverse events were assessed as nonserious. At the end of treatment, all patients (100%) in the active treatment group judged the subjective tolerability of EPs as good or very good.\n EPs represents an effective treatment of the common cold. It significantly reduces the severity of symptoms and shortens the duration of the common cold compared with placebo. The herbal drug is well tolerated.", "Chronic rhinosinusitis (CRS) is a recalcitrant inflammatory process which has a marked detrimental impact on quality of life. At the present there is no cure for this condition, measures are taken to stop progression, and provide symptomatic relief. Topical corticosteroids are commonly prescribed in the management of CRS, but few trials show effectiveness in clinical settings. We set up a randomized, double-blind, placebo-controlled trial to study the effectiveness of a topical corticosteroid agent--fluticasone propionate aqueous nasal spray (FPANS) in patients with CRS. We measured symptoms, diary card, and rigid endoscopy scores, acoustic rhinometry, middle meatal swabs, blood tests--CRP, ESR, WBC, and eosinophil count. Measurements were done at the start of the trial, at 8 weeks, and 16 weeks where possible. Twenty-two patients completed the trial, 9 received FPANS, and 13 had placebo. There was no difference between the 2 groups on all counts. When patients were considered as one group, there was an improvement in the diary card scores (p = 0.054), comparing baseline to 8 or 16 weeks. There was no evidence that the regular use of topical corticosteroid increased the risk of developing an infection. An important observation was that the topical corticosteroid did not precipitate acute sinusitis. There is compelling evidence that topical corticosteroids down-regulate cytokine expression, and it is likely that a larger, and longer multi-centre trial may prove their efficacy in CRS." ]

[ "8331703", "19477503", "9161392", "6195948", "8598656", "3672322", "6733063", "7717832", "8129501" ]

[ "Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups.", "Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial.", "A randomized, prospective trial of deep venous thrombosis prophylaxis in aortic surgery.", "Prevention of postoperative deep venous thrombosis and pulmonary emboli with combined modalities.", "Is DVT prophylaxis overemphasized? A randomized prospective study.", "Regimen for improved effectiveness of intermittent pneumatic compression in deep venous thrombosis prophylaxis.", "The efficacy of graduated compression stockings in the prevention of deep vein thrombosis after major gynaecological surgery.", "Deep vein thrombosis: prevention in stroke patients during rehabilitation.", "Changing clinical practice. Prospective study of the impact of continuing medical education and quality assurance programs on use of prophylaxis for venous thromboembolism." ]

[ "The incidence of deep venous thrombosis (DVT) and the efficacy of prophylactic measures were prospectively evaluated in all patients admitted to a level I trauma center during 1991. Patients with Injury Severity Scores (ISS) > 9 who survived a minimum of 48 hours (n = 395) were monitored using venous Doppler and ultrasound studies during hospitalization (total, 1308 studies). Two hundred eighty-one patients (71%) were randomly assigned to low-dose heparin or sequential compression devices. There were 18 cases of lower extremity DVT (4.6%) and four cases (1.0%) of pulmonary emboli (PE), three of which were fatal. Eight patients (2.9%) on prophylaxis and 10 (8.8%) without prophylaxis developed DVT (p < 0.02 by Chi-square). There were two PEs in each group. Fourteen of these 18 patients sustained blunt trauma and included seven spinal fractures or subluxations (four paraplegic) and four severe head injuries. This represented 14.0% of 50 patients admitted with spinal injuries and 4.3% of 92 patients with severe head injuries. Compared with those with no neurologic injury (7 of 253 or 2.7%), the risk of DVT is significantly higher in the spinal injury patients (p < 0.001, Chi-square) and twice as high as in the head injury group, although not statistically significant (p = 0.4, Chi-square). Three of the four patients with penetrating trauma and DVT had venous injuries. We conclude that DVT prophylaxis can significantly reduce the incidence of DVT in trauma patients with ISS > 9. Patients with severe neurologic injuries (particularly spinal cord) are at high risk for DVT and PE and may be considered for a prophylactic Greenfield filter.", "Deep vein thrombosis (DVT) and pulmonary embolism are common after stroke. In small trials of patients undergoing surgery, graduated compression stockings (GCS) reduce the risk of DVT. National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence. We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke.\n In this outcome-blinded, randomised controlled trial, 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK, Italy, and Australia. Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7-10 days and, when practical, again at 25-30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is registered, number ISRCTN28163533.\n All patients were included in the analyses. The primary outcome occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio 4.18, 95% CI 2.40-7.27).\n These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results.\n Medical Research Council (UK), Chief Scientist Office of Scottish Government, Chest Heart and Stroke Scotland, Tyco Healthcare (Covidien) USA, and UK Stroke Research Network.", "To study the incidence of postoperative deep venous thrombosis (DVT) in patients undergoing elective aortic reconstruction and to determine if aggressive DVT prophylaxis would reduce the incidence of DVT in these patients.\n Randomized, prospective trial.\n University hospital and Veterans Affairs hospital.\n One hundred patients undergoing aortic reconstruction for aneurysmal or occlusive disease randomized to receive DVT prophylaxis (treatment group) or no prophylaxis (control group). Exclusion criteria included a history of DVT, long-term anticoagulant use, or a malignant neoplasm. During the study period, 12 patients were ineligible for follow-up. Ninety-eight patients completed the trial, including 50 patients in the treatment group and 48 patients in the control group. Two patients in the control group died postoperatively of unrelated causes.\n Patients in the treatment group received DVT prophylaxis using a combination of low-dose heparin sodium therapy (5000 U every 12 hours) and calf-length intermittent mechanical compression devices. Control patients received no DVT prophylaxis.\n The occurrence of acute lower extremity DVT diagnosed by interval venous duplex ultrasound scan surveillance performed on postoperative days 1, 3, and 7.\n The overall incidence of proximal DVT in this study was 2%. One case of DVT occurred in the treatment group, and the other one occurred in the control group. There was no statistically significant difference (P = .99) in the incidence of DVT between the 2 groups. One patients in the control group had a nonfatal pulmonary embolus (1% of the patients overall).\n The incidence of proximal DVT in patients undergoing elective aortic reconstruction is low compared with patients undergoing other major intraabdominal general surgical procedures. The use of aggressive DVT prophylaxis did not reduce the risk of postoperative proximal DVT in this study. The selective use of DVT prophylaxis in patients undergoing elective aortic surgery should be based on associated concomitant or evolving risk factors.", "Worldwide statistics reveal that 25 to 40 per cent of patients who are over the age of 40 years and operated on for 1 or more hours will develop a deep venous thrombosis (DVT). The studies reviewed in this paper were performed to evaluate several modalities and compare their effectiveness in preventing DVT in postoperative patients. In the first study, five modalities plus a control group were evaluated in 562 patients from five surgical specialties. The incidence of DVT in the control group was 35 per cent. Though most of the pharmacologic agents were effective in reducing the incidence of DVT, the antistasis devices (gradient elastic stockings and intermittent pneumatic compression) were most effective. The purpose of the second study was to evaluate the effectiveness of combining a pharmacologic drug with an antistasis modality. Deep venous thrombosis was virtually eliminated in this group of 328 patients. There was only a 1.5 per cent incidence of DVT in the treated population as compared to a 26.8 per cent incidence in the control group. Thus, it seems that combining one antistasis and one pharmacologic agent greatly reduces the incidence of lower extremity thrombi. I-125 fibrinogen scanning was the most sensitive test in detecting DVT and had an accuracy of 97 per cent.", "This study was designed to prospectively evaluate a previously published prognostic index for predicting deep venous thrombosis (DVT) in general surgical patients with conventional prophylaxis. Patients undergoing procedures of at least 1 hr duration (abdominal, thoracic, head and neck, inguinal) requiring general or spinal anesthetic were prospectively randomized into the following groups: Group 1, sequential pneumatic compression devices during surgery and 2 days postoperatively; Group 2, subcutaneous heparin (5000 U q 12 hr) starting 1 hr before surgery and for 7 days postop; Group 3, control group. All patients underwent duplex evaluation of bilateral lower extremity deep venous systems preoperatively and on postoperative Days 1, 3, and 30. In addition, a previously developed predictive DVT incidence indicator, the prognostic index (PI), was calculated for each patient. A total of 137 patients were entered into the study with 29 removed for patient/staff reasons. There were no differences in PI among the three groups at the 0.05 level (ANOVA). The distribution of risk factors for DVT including increased age, body size, hemoglobin (Hb), and colorectal procedures were distributed evenly among the groups. Additional factors such as diabetes, COPD, PVD, immobilization, and cancer were also evenly distributed among the groups. The PI predicted a 20% incidence of DVT. For Groups 1 (n = 25), 2 (n = 38), and 3 (n = 45) no DVTs were detected over the 30 days of study. During the study period, 8 DVTs were detected by duplex evaluation in general surgical patients not in the study (1.5%). In conclusion, in a prospective randomized study using sequential pneumatic compression devices, subcutaneous heparin or no prophylaxis in matched general surgical patients at moderate to high risk for thromboembolism, no DVTs occurred for up to 30 days. Furthermore, neither a PI nor other factors associated with DVT accurately predicted the incidence of DVT in this patient population.", "The incidence of deep venous thrombosis (DVT) was assessed in a series of 78 patients undergoing major surgical operations to compare the prophylactic effectiveness of intermittent sequential pneumatic compression alone with the simultaneous use of graduated compression stockings and intermittent sequential pneumatic compression. The diagnosis of DVT was determined with the I-125 fibrinogen-uptake test, Doppler ultrasound, maximum venous outflow by strain-gauge plethysmography, and contrast venography. The incidence of DVT in nonstockinged legs was 9% while that in the stockinged legs was 1%. The simultaneous use of graduated elastic compression stockings and intermittent pneumatic compression is more effective than pneumatic compression alone in the prevention of postoperative DVT.", "The efficacy of graduated compression stockings in the prevention of deep vein thrombosis (DVT) after major gynaecological surgery was investigated in a controlled randomized prospective trial in 196 patients who were greater than 35 years of age. The stockings were worn by 104 of the 196 patients throughout their stay in hospital, the other 92 patients did not wear the stockings (control group). All the patients were scanned for DVT postoperatively with the 125I-labelled fibrinogen test. None of the 104 patients who wore the stockings developed a thromboembolism, but four of the 92 control patients who did not wear the stockings had DVT. This difference between the two groups was statistically significant.", "Deep vein thrombosis (DVT) and subsequent pulmonary embolism (PE) is a major source of mortality and morbidity in stroke patients. This study was designed to determine the effectiveness of different prophylactic treatments in the prevention of DVT after a stroke in patients undergoing rehabilitation. An additional objective was the identification of risk factors for DVT in stroke in patients during rehabilitation. Three hundred and sixty patients, over a 3-year period, were randomly assigned to one of four groups: adjusted dose heparin, intermittent pneumatic compression (IPC), functional electrical stimulation (FES), or control. There was no significant difference in the development of DVT by treatment group. Patients with DVT on admission (prevalent, n = 61) were compared with the study patients (n = 360). Time interval (from stroke to admission) and lactic dehydrogenase (LDH) concentration were significant risk factors, as well as predictors, for development of DVT (p < .000). These results suggest that the longer a patient remains without DVT prophylaxis after a stroke, the greater the risk of developing DVT and this supports early prophylaxis before rehabilitation.", "To determine the effect of continuing medical education (CME) with and without a quality assurance component (CME+QA) on physician practices in the prevention of venous thromboembolism.\n A communitywide study was performed in 15 short-stay hospitals in central Massachusetts. The study population included 3158 patients in acute-care hospitals with multiple risk factors for venous thromboembolism. Study hospitals were randomly assigned to one of two educational strategies or to a control group that received no intervention.\n The proportion of patients at high risk for venous thromboembolism who received effective methods of prophylaxis increased significantly from 29% in 1986 to 52% in 1989 (P < .001). This increase was seen in all study groups: control hospitals, 40% to 51% (P < .001); CME hospitals, 21% to 49% (P < .0001); and CME+QA hospitals, 27% to 55% (P < .0001). The increase in prophylaxis use from 1986 to 1989 was significantly greater among patients cared for in hospitals whose physicians participated in a formal CME program (an increase of 28%) than in control hospitals (an increase of 11%) (P < .001). There was no significant difference in the use of prophylaxis in hospitals whose physicians received CME+QA interventions compared with hospitals whose physicians received CME interventions alone (identical increases of 28%).\n A formal CME program significantly increased the frequency with which physicians prescribed prophylaxis for venous thromboembolism. We believe the key factor in our CME interventions that motivated clinicians to change their practices was the provision of hospital-specific data demonstrating a compelling need for improvement. Despite the substantial investment by hospitals in QA, traditional QA intervention appeared to provide no additional benefit. Even after extensive CME/QA interventions, prophylaxis for venous thromboembolism remained underutilized, suggesting the need to develop new approaches to changing clinical practice." ]

[ "75438", "8142334", "3089466", "2754147", "8831855", "3693764", "11799376", "9560837", "8738513" ]

[ "A double-blind controlled crossover trial of an antigen-avoidance diet in atopic eczema.", "The immunological and long-term atopic outcome of infants born to women following a milk-free diet during late pregnancy and lactation: a pilot study.", "Effect of maternal dietary exclusion on breast fed infants with eczema: two controlled studies.", "Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study.", "Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years' follow-up.", "Development of atopic disease in babies whose mothers were receiving exclusion diet during pregnancy--a randomized study.", "Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant.", "Randomised controlled trial of advice on an egg exclusion diet in young children with atopic eczema and sensitivity to eggs.", "Allergen avoidance in infancy and allergy at 4 years of age." ]

[ "20 out of 36 children (aged two to eight years) with atopic eczema completed a twelve-week, double-blind, controlled, crossover trial of an egg and cows' milk exclusion diet. During the first and third four-week periods, patients on an egg and cows' milk exclusion diet received a soya-based milk substitute (trial period) or an egg and cows' milk preparation (control period). Response was assessed in terms of eczema activity, number of areas affected, pruritus, sleeplessness, and antihistamine usage while on the two diets. During the middle period patients resumed their normal diet to minimise any carry-over effect. 14 patients responded more favourably to the antigen-avoidance diet than to the control diet, whereas only 1 responded more favourably to the control diet than the trial diet. Patients experienced more benefit during the first diet period than the second, whatever the nature of the diet. There was no correlation between a positive prick test to egg and cows' milk antigen and response to the trial diet.", "Infants born to atopic parents have been found to be at high risk of allergy development. The present study investigated the effect of a maternal milk-free diet during late pregnancy and lactation on the immune response and allergy incidence in at-risk and control infants. Atopic mothers were randomly allocated into an intervention group (n 12) or an unrestricted-diet group (n14) and compared with non-atopic mothers following an unrestricted diet (n 12). The intervention involved a maternal milk-free diet during late pregnancy and lactation. Infants were followed up for 18 months postnatally. A significant fall in maternal serum beta-lactoglobulin (beta-Lg)-immunoglobulin G (IgG) antibody levels (P < 0.05) was observed after a 7-week milk-exclusion diet. In maternal and cord serum samples the levels of beta-Lg-IgG and alpha-casein-IgG antibodies were significantly correlated (r 0.89, P < 0.0001 and r 0.71, P < 0.001 respectively). Higher levels of beta-Lg-IgG (P < 0.05) were observed in the cord serum samples compared with paired maternal serum samples. Single-blind allergy assessment by a paediatrician at 12 and 18 months showed that the infants born in the non-atopic group had a significantly lower allergy incidence compared with the infants born in the atopic group following an unrestricted diet (P < 0.008 and P < 0.02 respectively). The allergy incidence in the infants born in the atopic diet group was significantly lower compared with that of the atopic group following an unrestricted diet (P < 0.04). It was observed that the atopic nature of the parents significantly affected the allergy incidence in their children. A trend towards a beneficial effect of a maternal milk-free diet during late pregnancy and lactation was also observed in infants born to atopic parents.", "Thirty seven breast fed infants with eczema were studied to see whether changes in their mothers' diets affected their skin condition. Nineteen mothers and babies took part in a double blind crossover trial of exclusion of egg and cows' milk, and 18 took part in open exclusion of 11 foods followed by double blind challenge to those mothers whose infants seemed to respond. Babies were examined at the beginning and end of each dietary period, and the extent and severity of the rash were given a numerical score. The eczema improved in six infants when their mothers avoided egg and cows' milk and worsened again when these were reintroduced. Two infants suffered gastrointestinal reactions after maternal ingestion of egg and cows' milk, one developing colitis. Maternal dietary exclusion seems to benefit some breast fed babies with eczema.", "The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cow's milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cow's milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group (p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life.", "A prospective case-control study is presented to assess an allergy prevention programme in children up to 36 months of age. Infants born at three maternity hospitals were followed from birth: 279 infants with high atopic risk (intervention group) were compared with 80 infants with similar atopic risk but no intervention (non-intervention group). The intervention programme included dietary measures (exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet) and environmental measures (avoidance of parental smoking in the presence of the babies, day care > 2 years of life). Mothers in this group who had insufficient breast milk were randomly assigned to one of two coded formulas: either a hydrolysed milk formula (Nidina HA, Nestlé) or a conventional adapted formula (Nan, Nestlé). Other environmental measures remained the same as for the breastfeeding mothers. The non-intervention group were either breastfed or received the usual Italian milk feeding and weaning diet, without environmental advice. The main outcome measures were anthropometric measurements and allergic disease manifestations. Normal anthropometric data were observed both in the intervention group and in the non-intervention group. The incidence of allergic manifestations was much lower in the intervention group than in the non-intervention group at 1 year (11.5 versus 54.4%, respectively) and at 2 years (14.9 versus 65.6%) and 3 years (20.6 versus 74.1%). Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non-intervention group from birth up to the second year of life, while urticaria and gastrointestinal disorders were only present in the non-intervention group in the first year of life. Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non-intervention group. Relapse of the same allergic symptom was less in the intervention group (13.0%) than in the non-intervention group (36.9%). In comparison to the non-intervention group, there were fewer intervention group cases with two or more different allergic symptoms (8.7 versus 32.6%), and they were more likely to avoid steroid treatment (0 versus 10.8%) and hospital admission (0 versus 6.5%). Babies in the non-intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group. In the intervention group the breastfed infants had the lowest incidence of allergic symptoms, followed by the infants fed the hydrolysed formula (ns). Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants, although less than their counterparts in the non-intervention group. Of the affected subjects in the intervention group, 80.4% were RAST and/or Prick positive to food or inhalant allergens. Total serum IgE values detected at birth in the intervention group were not predictive, but at 1 and 2 years of age, IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy. In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups. Of the various factors tested in the non-intervention group, the following were the most important in the pathogenesis of allergic symptoms: (i) formula implementation begun in the first week of life; (ii) early weaning (< 4 months); (iii) feeding beef (< 6 months); (iv) early introduction of cow's milk (< 6 months); and (v) parental smoking in the presence of the babies and early day care admission (< 2 years of life). All the preventive measures used in this study (exclusive breastfeeding and/or hydrolysed milk feeding, delayed and selective introduction of solid foods, and environmental advice) were effective at the third year of follow-up, greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions", "In a prospective, randomized study, we have monitored the effect of maternal abstention from cow's milk and egg on the development of atopy in babies. Two hundred twelve women were followed from midpregnancy. We report the occurrences of allergies in their babies up to 18 months of age, as assessed by skin prick testing, determination of serum IgE, questionnaires, and blinded physical examination by a pediatric allergist. Whatever the method that was used, there was no statistically significant difference between babies whose mothers received the \"diet\" or the \"nondiet.\" Other factors known to influence the risk of atopy like heredity, sex, month of birth, breast-feeding, and exposure to tobacco smoke, animal dandruff, and solid food did not differ between the groups. The mothers receiving the exclusion diet, by their own choice, had diminished their intake of milk and egg during lactation also, and therefore, their babies were significantly less exposed to cow's milk before 6 months. Still, atopy was equally abundant among their children. Thus, maternal elimination diet during late pregnancy did not protect the baby against allergy.", "The prevalence of atopic diseases is increasing throughout the Western world, and means of primary prevention are needed to reverse this trend. The role of breast-feeding, the best source of infant nutrition, in protection against atopic disease remains elusive. In this double-blinded, placebo-controlled study of 62 mother-infant pairs, it is shown that administering probiotics to the pregnant and lactating mother increased the immunoprotective potential of breast milk, as assessed by the amount of anti-inflammatory transforming growth factor beta2 (TGF-beta2) in the milk (2885 pg/mL [95% CI, 1624-4146] in mothers receiving probiotics vs 1340 pg/mL [95% CI, 978-1702] in mothers receiving placebo; P =.018). The risk of developing atopic eczema during the first 2 years of life in infants whose mothers received probiotics was significantly reduced in comparison with that in infants whose mothers received placebo (15% and 47%, respectively; relative risk, 0.32 [95% CI, 0.12-0.85]; P =.0098). Maternal atopy was a clear risk factor for atopic eczema in the infant. The infants most likely to benefit from maternal probiotic supplementation were those with an elevated cord blood IgE concentration. Administering probiotics during pregnancy and breast-feeding thus offers a safe and effective mode of promoting the immunoprotective potential of breast-feeding and provides protection against atopic eczema during the first 2 years of life.", "The role of exclusion diets in the management of atopic eczema in young children is uncertain. This randomised controlled trial evaluates the effect of excluding egg from the diet in young children with atopic eczema and sensitivity to eggs. Fifty-five such children were randomised either to a 4-week regimen, in which mothers were given general advice on care of eczema and additional specific advice from a dietician about an egg exclusion diet (diet group), or to a control group in which general advice only was given. Both groups continued conventional topical treatment. Disease activity was assessed by estimates of the surface area affected by eczema and by an arbitrary severity score. Possible egg sensitivity was identified by RAST before randomisation and after the trial by double-blind placebo-controlled egg challenge.\n The mean reduction in surface area affected by eczema was significantly greater (p = 0.02) in the group receiving dietary advice (from 19.6% to 10.9% area affected) than in the control group (from 21.9% to 18.9%). A significant improvement also occurred in severity score (p = 0.04): from 33.9 to 24.0 units for the diet group compared with a decrease from 36.7 to 33.5 in the control group. The study suggests that advice on the dietary exclusion of eggs is useful as part of the overall management of young children with atopic eczema and sensitivity to eggs.", "In an attempt to prevent or reduce the manifestations of atopic disease, a group of infants considered to be genetically at high risk of atopy was entered in a prenatally randomized, controlled study. A prophylactic group (n = 58) was either breast-fed with their mothers excluding foods regarded as highly antigenic from their diets, or given an extensively hydrolysed formula. In addition, strenuous efforts were made to reduce exposure to the house-dust mite by application of acaricide to the bedroom and living room carpets and upholstered furniture. A control group (n = 62) was fed conventionally by breast or on formula, and no specific environmental measures were taken. The results (previously reported) after 1 year showed significantly less total allergy, asthma, and eczema in the prophylactic group. Similar results were obtained at 2 years although the reduction in asthma no longer achieved statistical significance. However, there was significantly less sensitization, as shown by a battery of skin prick tests (SPTs), to both dietary allergens and aeroallergens in the prophylactic group. All the children have now been reviewed at the age of 4 years, and SPTs to a wide range of dietary allergens and aeroallergens have been performed. The control group continues to show more total allergy (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.21-6.13, P < 0.02), definite allergy (allergic symptoms plus positive SPT) (OR 5.6, CI 1.8-17.9, P < 0.005), and eczema (OR 3.4, CI 1.2-10.1, P < 0.05). More control children have positive SPTs (OR 3.7, CI 1.3-10.0, P < 0.02). A dual approach to the prevention of allergic disease, avoiding as far as possible sensitization to food and aeroallergens, significantly reduces the risk of atopic disease. This should be reserved for infants considered at very high risk of atopy, and close medical and dietetic supervision must be available." ]

[ "7972781", "9159625", "1987387", "16765759", "15489085", "10514159", "11786451", "19528337", "3555690" ]

[ "Low-dose aspirin combined with dipyridamole versus anticoagulants after femoropopliteal percutaneous transluminal angioplasty.", "Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical prosthetic heart valves.", "Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.", "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.", "Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.", "Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin.", "Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.", "Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study.", "Random control trial of a short course of aspirin and dipyridamole (Persantin) for femorodistal grafts." ]

[ "To investigate whether anticoagulation or platelet inhibition treatment provides better prevention of reobstruction after percutaneous transluminal angioplasty (PTA).\n In a controlled study, 160 patients received either oral anticoagulants or a combination of low-dose acetylsalicylic acid (25 mg) and dipyridamole (200 mg) (ASAD) twice daily for 1 year after successful femoropopliteal PTA. Compliance was comparable. The patients in the two groups had similar clinical and angiographic characteristics. Patency was assessed with noninvasive methods 1 day and then 3, 6, and 12 months after PTA and was confirmed at angiography at the end of the study in 112 patients.\n Patency in patients who received anticoagulants was 53% and was not statistically significantly different from 69% in patients who received ASAD (P = .18). With anticoagulants, there were four bleeding complications (one was fatal); with ASAD, only five minor complications occurred.\n ASAD is at least as effective as anticoagulants for secondary prevention of obstruction after PTA but has less severe side effects.", "Mechanical heart valve replacement requires lifelong anticoagulant treatment. Aspirin has proved useful in further reducing thromboembolic events when added to oral anticoagulants. However, increased (gastrointestinal) bleeding was observed at the doses previously tested for this combination in heart valve prostheses.\n We performed a prospective randomized trial to compare the combination of low-intensity oral anticoagulants (international normalized ratio 2.5 to 3.5) plus aspirin (100 mg/day) (arm A) versus high-intensity oral anticoagulants alone (arm B) (international normalized ratio 3.5 to 4.5). Arm A included 258 patients and arm B 245 patients. The two groups were comparable for all baseline characteristics.\n The outcomes of the study were embolism, valve thrombosis, and major hemorrhage. The median follow-up was 23 months. The two treatments offered similar antithrombotic protection. The incidence of embolic episodes was 1.32 per 100 patient-years (95% confidence interval 0.53 to 2.7) for arm A and 1.48 per 100 patient-years (95% confidence interval 0.59 to 3.03) for arm B. Major hemorrhage occurred in 1.13 per 100 patient-years (95% confidence interval 0.41 to 2.45) for arm A and 2.33 per 100 patient-years (95% confidence interval 1.17 to 4.14) for arm B. Gastrointestinal bleeding was not increased by this combined reduced dose of aspirin and coumarin.", "To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease.", "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.", "This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.\n Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.\n We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.\n Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.\n The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.", "To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice.\n Randomised controlled trial.\n 729 patients aged >/=60 years with atrial fibrillation, recruited in general practice, who had no established indication for coumarin. Mean age was 75 years and mean follow up 2. 7 years.\n Primary care in the Netherlands.\n Patients eligible for standard intensity coumarin (international normalised ratio 2.5-3.5) were randomly assigned to standard anticoagulation, very low intensity coumarin (international normalised ratio 1.1-1.6), or aspirin (150 mg/day) (stratum 1). Patients ineligible for standard anticoagulation were randomly assigned to low anticoagulation or aspirin (stratum 2).\n Stroke, systemic embolism, major haemorrhage, and vascular death.\n 108 primary events occurred (annual event rate 5.5%), including 13 major haemorrhages (0.7% a year). The hazard ratio was 0.91 (0.61 to 1.36) for low anticoagulation versus aspirin and 0.78 (0.34 to 1.81) for standard anticoagulation versus aspirin. Non-vascular death was less common in the low anticoagulation group than in the aspirin group (0.41, 0.20 to 0.82). There was no significant difference between the treatment groups in bleeding incidence. High systolic and low diastolic blood pressure and age were independent prognostic factors.\n In a general practice population (without established indications for coumarin) neither low nor standard intensity anticoagulation is better than aspirin in preventing primary outcome events. Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice.", "To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.\n Collaborative meta-analyses (systematic overviews).\n Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen.\n 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens.\n \"Serious vascular event\": non-fatal myocardial infarction, non-fatal stroke, or vascular death.\n Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000.\n Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.", "Inhibition of platelet aggregation after aspirin or clopidogrel intake varies greatly among patients, and previous studies have suggested that poor response to oral antiplatelet agents may increase the risk of thrombotic events, especially after coronary angioplasty. Whether this reflects suboptimal platelet inhibition per se, which might benefit from more potent antiplatelet agents such as tirofiban, is unknown.\n We screened 1277 patients to enroll 93 aspirin, 147 clopidogrel, and 23 dual poor responders, based on a point-of-care assay, who underwent elective coronary angioplasty at 10 European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double-blind manner to receive either tirofiban (n=132) or placebo (n=131) on top of standard aspirin and clopidogrel therapy. The primary end point, consisting of troponin I/T elevation at least 3 times the upper limit of normal, was attained in 20.4% (n=27) in the tirofiban group compared with 35.1% (n=46) in the placebo group (relative risk, 0.58; 95% confidence interval, 0.39 to 0.88; P=0.009). The rate of major adverse cardiovascular events within 30 days in the tirofiban group also was reduced (3.8% versus 10.7%; P=0.031). The overall incidence of bleeding was low, likely explained by a substantial use of the transradial approach, and did not differ between the 2 groups.\n In low-risk patients according to clinical presentation who had poor responsiveness to standard oral platelet inhibitors via a point-of-care assay, intensified platelet inhibition with tirofiban lowers the incidence of myocardial infarction after elective coronary intervention.", "The effect of a short course of anti-platelet agents, started preoperatively, on the patency of femorodistal bypass grafts is unknown. One hundred and forty-eight such grafts were randomized to act as controls or to receive dipyridamole 200 mg b.d. for 48 h pre-operatively and dipyridamole 200 mg b.d. with aspirin 300 mg daily for 6 weeks after surgery. Patients were well-matched and the mean pre-operative pressure index of 0.37 rose to 0.78 during the first postoperative week. No deaths were attributable to the treatment. Ninety-three grafts were autogenous vein and the remainder were prosthetic (GORE-TEX (PTFE), human umbilical vein or externally supported Dacron). At 1 year autogenous vein cumulative patency was 75 per cent. Overall results showed higher patency in the treated group (P = 0.012) which was entirely accounted for by the difference between prosthetic dipyridamole and aspirin group (85 per cent patency) and prosthetic control groups (53 per cent patency, P = 0.005) and arose during the first postoperative month. There were 11 deaths and 8 amputations in the dipyridamole and aspirin group and 8 deaths and 12 amputations in the control group. It is concluded that a six week perioperative course of dipyridamole and aspirin allows the patency of prosthetic femorodistal bypass to approach that of autogenous vein, and the regimen therefore is recommended for patients who may require a prosthetic graft." ]

[ "2030245", "17663611", "11680554", "1460157", "17076751", "7673531", "10396792", "22443839", "16392991" ]

[ "A comparative evaluation of parent-training interventions for families of chronic delinquents.", "An adaptive approach to family intervention: linking engagement in family-centered intervention to reductions in adolescent problem behavior.", "Reducing conduct problems among children of battered women.", "Family preservation using multisystemic therapy: an effective alternative to incarcerating serious juvenile offenders.", "Randomised controlled trial of a parenting intervention in the voluntary sector for reducing child conduct problems: outcomes and mechanisms of change.", "Preventing escalation in problem behaviors with high-risk young adolescents: immediate and 1-year outcomes.", "An experimental intervention with families of substance abusers: one-year follow-up of the focus on families project.", "A family intervention to reduce sexual risk behavior, substance use, and delinquency among newly homeless youth.", "Intervention outcomes for girls referred from juvenile justice: effects on delinquency." ]

[ "Fifty-five families of chronically offending delinquents were randomly assigned to parent-training treatment or to service traditionally provided by the juvenile court and community. The families in the parent-training group received an average of 44.8 hours of professional contact (23.3 hours of which were phone contacts), and each control group family received treatment estimated at more than 50 hours on the average. Comparisons of police contact data at baseline and subsequent years for the two groups showed that subjects in both groups demonstrated reduced rates of offending during the followup years. The finding most relevant was significant treatment-by-time effect for offense rates, with most of this effect accounted for by a greater reduction in serious crimes for the experimental group during the treatment year, and a similar reduction of the community control group occurring in the first of three followup years. These early decrements in offense rates persisted during followup for both groups. Throughout the study, boys in the experimental group spent significantly less time in institutional settings than did boys in the control group. Parent training had a significant impact, but the reduction in offending was produced at very high emotional cost to staff. Although it is clear that this population requires substantial treatment resources, this study underscores the need for more work on prevention.", "This study used Complier Average Causal Effect analysis (CACE; see G. Imbens & D. Rubin, 1997) to examine the impact of an adaptive approach to family intervention in the public schools on rates of substance use and antisocial behavior among students ages 11-17. Students were randomly assigned to a family-centered intervention (N = 998) in 6th grade and offered a multilevel intervention that included (a) a universal classroom-based intervention, (b) the Family Check-Up (selected; T. J. Dishion & K. Kavanagh, 2003), and (c) family management treatment (indicated). All services were voluntary, and approximately 25% of the families engaged in the selected and indicated levels. Participation in the Family Check-Up was predicted by 6th-grade teacher ratings of risk, youth reports of family conflict, and the absence of biological fathers from the youths' primary home. Relative to randomized matched controls, adolescents whose parents engaged in the Family Check-Up exhibited less growth in alcohol, tobacco, and marijuana use and problem behavior during ages 11 through 17, along with decreased risk for substance use diagnoses and police records of arrests by age 18.", "This study was an experimental evaluation of an intervention designed to reduce conduct problems among children of battered women. Participants were 36 families (mothers and children) in which the mother had sought shelter because of relationship violence and had at least 1 child (4-9 years old) with clinical levels of conduct problems. The intervention consisted of 2 primary components: (a) providing instrumental and emotional support and (b) teaching child management skills to mothers. Families were randomly assigned to either the intervention condition or the existing services comparison condition and were assessed on 5 occasions over 16 months after shelter departure. Compared with families receiving existing services, children in the intervention condition improved at a faster rate, the proportion of children displaying clinical levels of conduct problems was greatly diminished, and mothers displayed greater improvements in child management skills.", "Multisystemic therapy (MST) delivered through a community mental health center was compared with usual services delivered by a Department of Youth Services in the treatment of 84 serious juvenile offenders and their multiproblem families. Offenders were assigned randomly to treatment conditions. Pretreatment and posttreatment assessment batteries evaluating family relations, peer relations, symptomatology, social competence, and self-reported delinquency were completed by the youth and a parent, and archival records were searched at 59 weeks postreferral to obtain data on rearrest and incarceration. In comparison with youths who received usual services, youths who received MST had fewer arrests and self-reported offenses and spent an average of 10 fewer weeks incarcerated. In addition, families in the MST condition reported increased family cohesion and decreased youth aggression in peer relations. The relative effectiveness of MST was neither moderated by demographic characteristics nor mediated by psychosocial variables.", "To test effectiveness of a parenting intervention, delivered in a community-based voluntary-sector organisation, for reducing conduct problems in clinically-referred children.\n Randomised controlled trial, follow-up at 6, 18 months, assessors blind to treatment status. Participants--76 children referred for conduct problems, aged 2-9, primarily low-income families, randomised to treatment vs. 6-month wait-list group. Retention was 93% at 6 months, 90% at 18 months. Interventions--Webster-Stratton Incredible Years video-based 14-week group programme, teaches cognitive-behavioural principles for managing behaviour, using a collaborative, practical, problem-solving approach. Primary outcomes--child problem behaviour by parent-report (Eyberg) and home-based direct observation; secondary outcomes--observed positive and negative parenting; parent-reported parenting skill, confidence and depression.\n Post-treatment improvements were found in child problem behaviour, by parent-report (effect size (ES) .48, p = .05) and direct observation (ES .78, p = .02); child independent play (ES .77, p = .003); observed negative (ES .74, p = .003) and positive (ES .38, p = .04) parenting; parent-reported confidence (ES .40, p = .03) and skill (ES .65, p =.01), using ANCOVA to control for baseline scores. Maternal depression did not change. Consumer satisfaction was high. At 18-month follow-up, although no randomised comparison was possible, changes appeared to maintain, with no significant change toward baseline level on any measure. Change in observed positive parenting appeared to mediate change in child problem behaviour (p < .025).\n Findings suggest that a group-based cognitive-behavioural parenting programme, delivered by well-trained and supervised staff, can be effective in a community voluntary-sector setting, for reducing conduct problems and enhancing parenting skills. Change in parenting skill appears to be a key mechanism for change in child behaviour. Findings have implications for feasibility of translating evidence-based programmes, even for clinically-referred conduct problems, into less specialised community settings, likely to have lower costs and be more accessible for families.", "The study tested alternative intervention strategies to reduce escalation in problem behaviors among high-risk young adolescents (11 to 14 years old). A total of 158 families with young adolescents (male and female) participated in this study. Of these, 119 families were randomly assigned to 1 of the following intervention conditions: (a) parent focus, (b) teen focus, (c) parent and teen focus, (d) self-directed change (materials only). In addition, 39 families of young adolescents were recruited as a quasi-experimental control. Parent focus and teen focus interventions resulted in immediate beneficial effects in observed and reported family conflict. The parent intervention conditions showed immediate beneficial effects on behavior problems at school. Longitudinal trends suggest that the parent focus condition may reduce subsequent tobacco use, compared with all other approaches. Interventions that aggregated high-risk youths into groups, however, showed the highest escalations in tobacco use and problem behavior at school, beginning at termination and persisting to follow-up. These findings are discussed with respect to the need to re-evaluate strategies that aggregate high-risk youths into intervention programs and focus more on strategies to engage parents in prevention.", "Children whose parents abuse drugs are exposed to numerous factors that increase the likelihood of future drug abuse. Despite this heightened risk, few experimental tests of prevention programs with this population have been reported. This article examines whether intensive family-focused interventions with methadone treated parents can reduce parents' drug use and prevent children's initiation of drug use.\n Parents were assigned randomly into intervention and control conditions and assessed at baseline, post-test, and 6 and 12 months following the intervention. Children were assessed at baseline, and 6- and 12-month follow-up points.\n Two methadone clinics in Seattle, Washington.\n One hundred and forty-four methadone-treated parents, and their children (n = 178) ranging in age from 3 to 14 years old.\n The experimental intervention supplemented methadone treatment with 33 sessions of family training combined with 9 months of home-based case management. Families in the control condition received no supplemental services.\n Parent measures included: relapse and problem-solving skills, self-report measures of family management practices, deviant peer networks, domestic conflict and drug use. Child measures included self-report measures of rules, family attachment, parental involvement, school attachment and misbehavior, negative peers, substance use and delinquency.\n One year after the family skills training, results indicate significant positive changes among parents, especially in the areas of parent skills, parent drug use, deviant peers and family management. Few changes were noted in children's behavior or attitudes.\n Programs such as this may be an important adjunct to treatment programs, helping to strengthen family bonding and to reduce parents' drug use.", "We evaluate the efficacy of a short family intervention in reducing sexual risk behavior, drug use, and delinquent behaviors among homeless youth.\n A randomized controlled trial of 151 families with a homeless adolescent aged 12 to 17 years. Between March 2006 and June 2009, adolescents were recruited from diverse sites in Southern California and were assessed at recruitment (baseline), and at 3, 6, and 12 months later. Families were randomly assigned to an intervention condition with five weekly home-based intervention sessions or a control condition (standard care). Main outcome measures reflect self-reported sexual risk behavior, substance use, and delinquent behaviors over the past 90 days.\n Sexual risk behavior (e.g., mean number of partners; p < .001), alcohol use (p = .003), hard drug use (p < .001), and delinquent behaviors (p = .001) decreased significantly more during 12 months in the intervention condition compared with the control condition. Marijuana use, however, significantly increased in the intervention condition compared with the control condition (p < .001).\n An intervention to reengage families of homeless youth has significant benefits in reducing risk over 12 months.\n Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.", "An increasing number of girls are entering the juvenile justice system. However, intervention programs for delinquent girls have not been examined empirically. The authors examined the 12-month outcomes of a randomized intervention trial for girls with chronic delinquency (N = 81). Girls were randomly assigned into an experimental condition (Multidimensional Treatment Foster Care; MTFC) or a control condition (group care; GC). Analyses of covariance indicated that MTFC youth had a significantly greater reduction in the number of days spent in locked settings and in caregiver-reported delinquency and had 42% fewer criminal referrals than GC youth (a trend) at the 12-month follow-up. Implications for reducing girls' chronic delinquency are discussed." ]

[ "2691402", "12269458", "6365424", "7822059", "7005653", "3060308", "2403486", "6572128", "6754242" ]

[ "Clinical trial of a low-fluoride toothpaste for young children.", "A randomised controlled trial of the effectiveness of providing free fluoride toothpaste from the age of 12 months on reducing caries in 5-6 year old children.", "Caries prevention using a 1.2% sodium monofluorophosphate dentifrice in an aluminium oxide trihydrate base.", "Enamel opacities and dental caries in children who used a low fluoride toothpaste between 2 and 5 years of age.", "[Cariostatic effect of Fluocaril; controlled clinical research].", "A 3-year oral health dose-response study of sodium monofluorophosphate dentifrices with and without zinc citrate: anti-caries results.", "Caries-preventive effect of fluoride dentifrices with and without anticalculus agents: a 3-year controlled clinical trial.", "Combined effects of a fluoride dentifrice and mouthrinse on the incidence of dental caries.", "Comparative unsupervised clinical trial on caries inhibition effect of monofluorophosphate and amine fluoride dentifrices after 3 years in Strasbourg, France." ]

[ "In this double-blind trial, the anticaries effectiveness of a test toothpaste formulated for young children with 550 ppm F was compared with that of a positive control toothpaste containing 1055 ppm fluoride. More than 3000 2-year-old children were enrolled in the study and after 3 years of toothpaste use, 2177 (72 per cent) were examined. From a clinical and radiographic assessment, more than half the children were found to be caries free and only 32 (1.5 per cent) had evidence of rampant caries. There appeared to be little or no difference between children who had used test or control pastes, either in caries or in plaque levels. On the basis of this clinical trial the experimental toothpaste with 550 ppm fluoride would appear to have a similar anticaries efficacy to that of the control toothpaste. Differences were seen in relation to sex of the child and to social class. Girls had lower levels of plaque than boys but more carious teeth. Children from families in higher social classes had fewer carious teeth and lower levels of plaque.", "To assess the impact of regularly supplying free fluoride toothpaste regularly to children, initially aged 12 months, and living in deprived areas of the north west of England on the level of caries in the deciduous dentition at 5-6 years of age. A further aim was to compare the effectiveness of a programme using a toothpaste containing 440 ppmF (Colgate 0-6 Gel) with one containing 1,450 ppmF (Colgate Great Regular Flavour) in reducing caries.\n Randomised controlled parallel group clinical trial. Clinical data were collected from test and control groups when the children were 5-6 years old.\n A programme of posting toothpaste with dental health messages to the homes of children initially aged 12 months. Clinical examinations took place in primary schools.\n 7,422 children born in 3-month birth cohorts living in high caries areas in nine health districts in north west England. Within each district children were randomly assigned to test or control groups.\n Toothpaste, containing either 440 ppmF or 1450 ppmF, and dental health literature posted at three monthly intervals to children in test groups until they were aged 5-6 years.\n The dmft index, missing teeth and the prevalence of caries experience.\n An analysis of 3,731 children who were examined and remained in the programme showed the mean dmft to be 2.15 for the group who had received 1,450 ppmF toothpaste and 2.49 for the 440 ppmF group. The mean dmft for the control group was 2.57. This 16% reduction between the 1,450 ppmF and control group was statistically significant (P<0.05). The difference between the 440 ppmF group and control was not significant. Further analyses to estimate the population effect of the programme also confirmed this relationship.\n This study demonstrates that a programme distributing free toothpaste containing 1,450 ppmF provides a significant clinical benefit for high caries risk children living in deprived, non-fluoridated districts.", "A 3-year clinical trial was carried out in France just after fluoride toothpaste was allowed to be sold on the mass market. The aim was to assess the caries preventive effect of a toothpaste containing the maximum fluoride level permitted by the EEC (1.2% SMFP). The trial started with 1318 10-12-yr-old children from a wide socioeconomic background in a typical French community. Test toothpaste was given to 659 children whereas the remaining 659 children obtained the same toothpaste without the fluoride additive. The brushing was unsupervised and performed by the children at home. Dental caries was assessed by clinical and radiographic examinations. 1061 children completed the trial. An interview carried out at the final examination identified a group of 116 uncooperative children (less than five brushings a week on average) who were not included in the statistical analysis. The following mean reductions were found: 26% for DMFT, 27% for DMFS, and 39% for DMFSU. The DMFS index for approximal, buccal-lingual and occlusal surfaces showed caries reductions of 32%, 25%, and 22%, respectively. The trial demonstrated a highly significant effectiveness of the 1.2% SMFP toothpaste in a French population.", "A recent clinical trial investigated the cariostatic effectiveness of a low (550 ppm) fluoride toothpaste in comparison with a standard (1050 ppm) control paste in pre-school children who were 2-years-old at the start of the 3-year trial. The present study has investigated the prevalence of enamel opacities in permanent incisor teeth and of caries in children who had taken part. As well as children from test and control groups, a third group of non-trial children were included in the sample. A total of 1,523 children were examined in schools and had photographs taken of their upper permanent incisor teeth. The latter were scored using the Thylstrup and Fejerskov (TF) index for fluorosis and the modified Developmental Defects of Enamel (DDE) index. Differences between the groups were small in real terms but using the TF index the child and tooth prevalence of opacities were significantly lower in the children who had used the test paste with a lower fluoride content; the same trend was seen in diffuse defects scored using the modified DDE index. There was no significant difference in the prevalence of caries in either primary or permanent teeth although the trend in both cases was for slightly more disease in children who had used the test paste.", "A controlled, double-blind trial on 42 children showed that a dentrifrice containing 0,25% fluorine clearly prevented caries when used continuously for 2 years. This effects was greater than that of a similar toothpaste containing fluorine. Tolerance was excellent.", "A 3-yr clinical trial has been conducted on 3000 12-yr-old children in Lanarkshire, Scotland, with the aim of investigating the effects on oral health of toothpastes containing both sodium monofluorophosphate and zinc citrate, the former being present at fluoride levels of 1000, 1500, and 2500 ppm F. No significant difference in caries increments was found between the group of children using toothpastes incorporating zinc citrate and their counterparts using zinc-free pastes. However, a significant anti-caries dose-response was demonstrated over the SMFP range used. This dose-response was evident for boys and girls and also for the various types of teeth and tooth surfaces.", "A 3-year, double-blind, randomized caries trial was conducted to evaluate the relative anticaries efficacy of four sodium fluoride dentifrices containing 250 ppm fluoride, 1,000 ppm fluoride in combination with 1% disodium 1-hydroxyethylidene-1.1-bisphosphonate (HEBP), and 1,000 ppm fluoride in combination with 1% disodium azacycloheptylidene-2.2-bisphosphonate (AHBP). As a positive control, a monofluorophosphate dentifrice (1,000 ppm fluoride) was used. At outset 1,161 Icelandic children, 11 and 12 years of age, were randomly assigned to one of the five treatment groups and 1,035 subjects completed the trial. After 3 years of unsupervised brushing, the dentifrice containing 250 ppm fluoride was significantly less effective in controlling the caries increment. The combination of sodium fluoride and AHBP was significantly more effective than the positive control.", "751 14- and 15-year old children completed a 3-year, double-blind, caries preventive program. The effects of daily, supervised toothbrushing with an 0.76% sodium monofluorophosphate dentifrice, rinsing with a 0.05% sodium fluoride mouthrinse, and the combined effects of the two treatments were investigated. Both the dentifrice and mouthrinse reduced the incidence of dental caries, but their combined use at the same time had no greater effect than either used alone.", "A randomized, double blind clinical trial of the caries inhibition effects of dentifrices containing respectively monofluorophosphate and amine fluoride was performed. A third control group used a toothpaste without fluoride. A total number of 2008 schoolchildren ranging in age from 6 to 8 years and living in Strasbourg (France) participated in this study. After a baseline examination three groups were constructed with the block randomization technic. The caries inhibition effects of the three dental pastes were compared after 3 years of unsupervised use. The monofluorophosphate dentifrice showed a reduction of 7.02% for DMFT, 5.17% for DMFS and 25.26% for the df rate. The reduction of amine fluoride dentifrice caries was respectively 21.62% for DMFT, 20.94% for DMFS and 48.66% for the df rate." ]

[ "18341378", "12789464", "9817273", "17214057", "11013273", "19634161", "11849797", "10725619", "10829042" ]

[ "Limited cytoprotective effects of amifostine in high-dose radioactive iodine 131-treated well-differentiated thyroid cancer patients: analysis of quantitative salivary scan.", "Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection?", "Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study.", "Effect of Amifostine to prevent radiotherapy-induced acute and late toxicity in head and neck cancer patients who had normal or mild impaired salivary gland function.", "Phase III randomized trial of amifostine as a radioprotector in head and neck cancer.", "Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer.", "Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer.", "A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma.", "Subcutaneous administration of amifostine during fractionated radiotherapy: a randomized phase II study." ]

[ "The aim of present study was to investigate the cytoprotective effect of amifostine on salivary glands in 131I-treated differentiated thyroid cancer (DTC) patients using serial quantitative analysis of salivary gland scans.\n Serial quantitative salivary scintigraphies were performed in 80 newly diagnosed DTC patients (9 men, 71 women; mean age, 43.2 years old; range, 21-58 years old). Forty-two patients were assigned randomly to the amifostine treatment group, which received 300 mg/m2 amifostine intravenously before 131I administration.\n In both amifostine-treated and nontreated groups statistically significant declines of functional parameters after 131I treatment were revealed by quantitative salivary scintigraphy in DTC patients. Amifostine pretreatment did not prevent the parenchymal damage to major salivary gland function after 131I treatment (F = 1.37, p = 0.2461). However, the dose of 131I had significant effects on salivary gland function after 131I treatment (F = 9.72, p = 0.0002).\n The present study did not show cytoprotective effects of amifostine for DTC patients treated with 131I.", "Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer.\n 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m(2) carboplatin, day 1-5 in week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation.\n 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis.\n According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary.", "Salivary gland impairment is a well-recognized side effect following high-dose radioiodine treatment (HD-RIT). Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. Therefore, the effect of amifostine was studied in HD-RIT.\n Parenchymal function was assessed by quantitative salivary gland scintigraphy performed prospectively in 50 patients with differentiated thyroid cancer before and 3 months after HD-RIT with either 3 GBq iodine ((131)I) (n=21) or 6 GBq (131)I (n=29) in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously before HD-RIT and 25 patients served as controls, who received physiologic saline solution. Xerostomia was graded according to World Health Organization (WHO) criteria.\n Before HD-RIT in 25 control patients, uptake of technetium-99m (99mTc)-pertechnetate was 0.45%+/-0.16% and 0.42%+/-0.16% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function was significantly (P < .001) reduced by 40.2%+/-14.1% and 39.9%+/-15.3% in parotid and submandibular glands, respectively. Nine control patients developed grade I and two grade II xerostomia. In 25 amifostine-treated patients, uptake of 99mTc-pertechnetate was 0.46%+/-0.16% and 0.43%+/-0.17% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function of salivary glands was not significantly altered (P=.691) and xerostomia did not occur in any of these patients.\n Parenchymal damage in salivary glands caused by HD-RIT can significantly be reduced by amifostine, which may improve the quality of life of patients with differentiated thyroid cancer.", "Amifostine has a potential role for salivary gland protection in head and neck cancer patients who had radiotherapy.\n Sixty-seven head and neck cancer patients were randomized to receive radiotherapy or radiotherapy plus Amifostine. The efficacy of the treatment was determined by a questionnaire evaluating dryness of mouth and the oral comfort, the RTOG/EORTC acute/late radiation morbidity scoring criteria, collection of the whole saliva and the 99mTc-pertecnetate scintigraphy of the salivary glands.\n Amifostine significantly reduced the mean questionnaire scores from 6.49 to 3.73, the incidence of grade > or = 2 mucositis from 75% to 36% and acute xerostomia from 82% to 39%. The salivary gland function returned to normal at a rate of 36.3% in the Amifostine group versus 9.1% in the control group.\n Amifostine is effective in reducing the incidence and severity of acute mucositis, acute and late xerostomia in head and neck cancer patients.", "Radiotherapy for head and neck cancer causes acute and chronic xerostomia and acute mucositis. Amifositine and its active metabolite, WR-1065, accumulate with high concentrations in the salivary glands. This randomized trial evaluated whether amifostine could ameliorate these side effects without compromising the effectiveness of radiotherapy in these patients.\n Patients with previously untreated head and neck squamous cell carcinoma were eligible. Primary end points included the incidence of grade > or =2 acute xerostomia, grade > or =3 acute mucositis, and grade > or =2 late xerostomia and were based on the worst toxicity reported. Amifostine was administered (200 mg/m(2) intravenous) daily 15 to 30 minutes before irradiation. Radiotherapy was given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 Gy. Whole saliva production was quantitated preradiotherapy and regularly during follow-up. Patients evaluated their symptoms through a questionnaire during and after treatment. Local-regional control was the primary antitumor efficacy end point.\n Nausea, vomiting, hypotension, and allergic reactions were the most common side effects. Fifty-three percent of the patients receiving amifostine had at least one episode of nausea and/or vomiting, but it only occurred with 233 (5%) of 4,314 doses. Amifostine reduced grade > or =2 acute xerostomia from 78% to 51% (P<.0001) and chronic xerostomia grade > or = 2 from 57% to 34% (P=.002). Median saliva production was greater with amifostine (0.26 g v 0.10 g, P=.04). Amifostine did not reduce mucositis. With and without amifostine, 2-year local-regional control, disease-free survival, and overall survival were 58% versus 63%, 53% versus 57%, and 71% versus 66%, respectively.\n Amifostine reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.", "A randomized phase 2 study was performed to investigate the efficacy/toxicity of combining concomitant boost radiation and weekly carboplatin/paclitaxel with or without amifostine in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).\n Patients with newly diagnosed, locally advanced stage III or IV SCCHN received 4 weekly doses of carboplatin (area under the curve, 1.5) and paclitaxel (45 mg/m(2)) concurrently with concomitant boost radiation consisting of 72 grays in 42 fractions over 6 weeks (every day for 18 days, twice a day for 12 days) (grading determined according to the TNM staging system). All patients were randomized to subcutaneous daily amifostine at a dose of 500 mg (Arm A) or no amifostine (Arm B). Toxicity data were collected weekly, and saliva collection was performed with and without citric acid stimulation. To evaluate the correlation between serum cytokine levels and the severity of oral mucositis, we evaluated a subset (13 patients in Arm A and 11 patients in Arm B) of subjects at baseline and then on alternate weeks.\n Fifty-eight patients were enrolled, 29 in each arm. The majority of patients were men (90%), had stage IV disease (82%), and had the oropharynx as the primary tumor site (60%). Major toxicities encountered were similar in both arms and included grade 3 (as determined by Common Terminology Criteria for Adverse Events, version 3.0) mucositis (75% in Arm A and 70% in Arm B) and grade 2 xerostomia (41% in both arms). The median number of amifostine doses delivered was 28, with skin toxicity (grade 3 in 11 patients) as the limiting factor. Saliva production showed no difference between the arms. The median follow-up was 34 months, and only 5 failures had been encountered (2 local and 3 distant) at the time of last follow-up, with an overall survival rate of 89%. Neck dissection was performed in 25 patients; 5 patients demonstrated persistent disease and 4 patients were alive without disease recurrence at the time of last follow-up. The median time to percutaneous endoscopic gastrostomy removal was 9.6 months in Arm A and 10.4 months in Arm B. Only 1 patient remained percutaneous endoscopic gastrostomy-dependent at the time of last follow-up. A correlation was noted between levels of selected cytokines and mucositis severity, in which higher levels of proinflammatory cytokines (tumor necrosis factor, interleukin [IL]-1, and IL-6) and lower levels of anti-inflammatory cytokines (IL-13) were noted. No changes in C-reactive protein levels were noted.\n Four weekly doses of carboplatin/paclitaxel with concomitant boost radiation was found to be a highly effective regimen in this patient population with advanced SCCHN. The overall survival rate was 89%. The time to percutaneous endoscopic gastrostomy removal was prolonged. Amifostine given subcutaneously did not improve the rates of xerostomia and mucositis with this fairly intensive chemoradiotherapy regimen.\n 2009 American Cancer Society.", "To determine the prophylactic properties of amifostine against acute and late toxicities from radiochemotherapy in patients with head-and-neck cancer.\n Fifty patients were randomized to receive conventional radiotherapy (RT) (2-Gy fractions, 5 days weekly, to a total of 60-74 Gy, depending on the tumor localization and TNM classification) and carboplatin (90 mg/m(2) infusion once per week before RT). Amifostine (300 mg/m(2)) was administered in the study group only 15-30 min before RT for 6-7.5 weeks. The primary study end point was the grading of acute and late nonhematologic toxicities (mucositis, dysphagia, xerostomia) induced by radiochemotherapy. Secondary end points included treatment duration, hematologic toxicity, and clinical outcome.\n The treatment duration was significantly shorter in the amifostine-treated group (p = 0.013), because treatment interruptions were more frequent in the control group. Acute toxicities (mucositis and dysphagia) were less severe in the amifostine-treated group. By Week 3, all in the control group experienced Grade 2 mucositis compared with only 9% in the amifostine-treated group (p <0.0001). By Week 5, 52.2% of the patients in the control group experienced Grade 4 mucositis compared with 4.5% in the amifostine-treated group (p = 0.0006). Similar results were obtained for dysphagia. At 3 months of follow-up, only 27% of patients in the study group experienced Grade 2 xerostomia compared with 73.9% in the control group (p = 0.0001). Eighteen months after cessation of therapy, the proportion of patients with Grade 2 xerostomia was 4.5% vs. 30.4% for each respective treatment group (p = 0.047). Cytoprotection with amifostine did not affect treatment outcome, with 90.9% complete responses in the amifostine-treated group compared with 78.3% in the control group (p = 0.414).\n Amifostine was effective in reducing mucositis and dysphagia resulting from radiochemotherapy in patients with head-and-neck cancer. Furthermore, amifostine reduced the severity of late xerostomia, a side effect of RT with long-lasting consequences. Amifostine treatment did not affect the clinical outcome.", "The aim of this study was to assess whether amifostine could minimize acute mucositis induced by a very accelerated irradiation regimen in patients with advanced head and neck squamous cell carcinoma (HNSCC).\n Between May 1996 and February 1998, 26 patients with an inoperable nonmetastatic Stage IV HNSCC were entered in this study. The treatment consisted of very accelerated radiotherapy given 64 Gy in 3.5 weeks. The patients were randomized to receive or not 150 mg/m(2), amifostine (Ethyol, U.S. Bioscience) 15-30 min prior to each radiation session.\n Of the 13 patients who received amifostine, definitive interruption of amifostine occurred in 5 cases (38%), due to tolerance problems (vomiting, liver enzyme elevation, generalized erythema). The distribution of Grade 4 mucositis (WHO) was 1 case versus 8 cases, with and without amifostine, respectively. The mean duration of \"at least Grade 3\" mucositis (WHO) was 25.1 days versus 49.2 days with and without amifostine (p = 0.03). In the amifostine group, 11/13 of the patients required a feeding tube (nasogastric tube or medical gastrostomy), because of acute mucositis, whereas in the control group a feeding tube was necessary in all cases. The mean duration of the use of this feeding tube was 1 month versus 2.5 months with and without amifostine respectively (p < 0.01). Local-regional control was not different between both arms with a median follow-up of 15 months.\n Despite the limited number of patients, this pilot randomized study suggests that amifostine was able to markedly reduce the severity and duration of mucositis induced by very accelerated radiotherapy. However, the tolerance of this twice daily amifostine schedule was relatively poor.", "Amifostine (WR-2721) is an important cytoprotective agent. Although intravenous administration is the standard route, pharmacokinetic studies have shown acceptable plasma levels of the active metabolite of amifostine (WR-1605) after subcutaneous administration. The subcutaneous route, due to its simplicity, presents multiple advantages over the intravenous route when amifostine is used during fractionated radiotherapy.\n Sixty patients with thoracic, 40 with head and neck, and 40 with pelvic tumors who were undergoing radical radiotherapy were enrolled onto a randomized phase II trial to assess the feasibility, tolerance, and cytoprotective efficacy of amifostine administered subcutaneously. A flat dose of amifostine 500 mg, diluted in 2.5 mL of normal saline, was injected subcutaneously 20 minutes before each radiotherapy fraction.\n The subcutaneous amifostine regimen was well tolerated by 85% of patients. In approximately 5% of patients, amifostine therapy was interrupted due to cumulative asthenia, and in 10%, due to a fever/rash reaction. Hypotension was never noted, whereas nausea was frequent. A significant reduction of pharyngeal, esophageal, and rectal mucositis was noted in the amifostine arm (P <.04). The delays in radiotherapy because of grade 3 mucositis were significantly longer in the group of patients treated with radiotherapy alone (P <.04). Amifostine significantly reduced the incidence of acute perineal skin and bladder toxicity (P <.0006).\n Subcutaneous administration of amifostine is well tolerated, effectively reduces radiotherapy's early toxicity, and prevents delays in radiotherapy. The subcutaneous route is much simpler and saves time compared with the intravenous route of administration and can be safely and effectively applied in the daily, busy radiotherapy practice." ]

[ "16394045", "17666597", "9065105", "2223679", "11134431", "11320043", "10735900", "15507957", "17272503" ]

[ "Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia.", "Antepartum treatment without early cordocentesis for standard-risk alloimmune thrombocytopenia: a randomized controlled trial.", "Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin.", "Idiopathic thrombocytopenic purpura in pregnancy: a randomized trial on the effect of antenatal low dose corticosteroids on neonatal platelet count.", "A randomized trial of granulocyte-macrophage colony-stimulating factor in neonates with sepsis and neutropenia.", "A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia.", "Use of recombinant human granulocyte colony-stimulating factor to increase chemotherapy dose-intensity: a randomized trial in very high-risk childhood acute lymphoblastic leukemia.", "Thromboprophylaxis and pregnancy: two randomized controlled pilot trials that used low-molecular-weight heparin.", "Bone marrow transplantation for severe aplastic anemia: a randomized controlled study of conditioning regimens." ]

[ "Antenatal therapy with intravenous immunoglobulin (IVIG) and prednisone has been shown to improve fetal thrombocytopenia and reduce the incidence of intracranial hemorrhage in neonatal alloimmune thrombocytopenia. Optimization of this therapy for individual patients, however, has yet to be achieved.\n In these parallel, randomized, multicenter studies, 78 patients in 79 pregnancies were stratified to 2 different treatment arms based on the presence of a peripartum intracranial hemorrhage in a previously affected sibling and/or the initial fetal platelet count. Patients with a history of an antenatal intracranial hemorrhage in a prior pregnancy were excluded.\n Forty women whose children from a previous birth had a peripartum intracranial hemorrhage or whose current fetus had an initial platelet count less than 20,000/mL3 were randomly assigned to receive IVIG plus prednisone or IVIG alone. The mean increase in fetal platelet counts in the following 3 to 8 weeks was 67,100/mL3 and 17,300/mL3, respectively (P < .001). Thirty-nine patients whose prior affected child did not have an intracranial hemorrhage and whose initial platelet count was more than 20,000/mL3 were randomly assigned to receive IVIG alone or prednisone alone. There were no significant differences, and 33 (85%) had birth platelet counts more than 50,000/mL3. There were 11 (6%) significant complications after a total of 175 fetal blood sampling procedures, 2 of which led to fetal or neonatal deaths.\n The spectrum of disease severity of alloimmune thrombocytopenia is reflected in the initial fetal platelet count and response to therapy. Fetal blood sampling may be associated with significant fetal/neonatal morbidity and mortality. Empiric therapy sufficient to treat the most severely affected fetuses will overtreat others and is likely to be associated with additional maternal morbidity.", "To evaluate the effectiveness and safety of two antenatal treatment regimens designed to optimally protect fetuses against intracranial hemorrhage resulting from alloimmune thrombocytopenia while minimizing the risks associated with fetal blood sampling. The study was limited to \"standard-risk\" patients, who were defined as women with documented alloimmune thrombocytopenia who had not delivered an infant with an intracranial hemorrhage in a prior pregnancy.\n In this prospective multicenter study of 73 women with documented alloimmune thrombocytopenia, patients were randomized to receive either intravenous immunoglobulin (IVIG) 2 g/kg/wk (group A) or IVIG 1 g/kg/wk plus prednisone 0.5 mg/kg/d (group B), starting at approximately 20 weeks of gestation. Fetal blood sampling was performed at approximately 32 weeks of gestation, and those with fetal platelet counts less than 30,000/mL(3) were given salvage therapy.\n There were two intracranial hemorrhages; neither was due to treatment failure. The average platelet counts at the time of fetal blood sampling were 121,600/mL(3) and 116,100/mL(3), and the average birth platelet counts were 169,400/mL(3) and 134,000/mL(3) for groups A and B, respectively. Twenty-seven percent of patients in group A and 17% in group B received salvage therapy, and only one neonate in each of these subsets had a birth platelet count less than 30,000/mL(3). There were four complications after 79 fetal blood sampling procedures, leading to cesarean deliveries between 32 and 37 weeks. There was a higher incidence of gestational diabetes and a tendency to more fluid retention, mood swings, insomnia, and jitteriness in patients on prednisone and of moderate-to-severe fatigue in those on high-dose IVIG alone.\n The outcomes of both treatment groups were excellent and comparable. Early cordocentesis is not necessary when treating alloimmune thrombocytopenia in patients who have not delivered an infant with an intracranial hemorrhage in a prior pregnancy.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00194987\n I.", "Our purposes were to investigate maternal infusions of intravenous gamma-globulin, to prevent intracranial hemorrhage, and to determine whether 1.5 mg dexamethasone and 60 mg prednisone per day add to the effect of intravenous gamma-globulin.\n Fifty-four women with alloimmune thrombocytopenia and thrombocytopenic fetuses were randomized to intravenous gamma-globulin 1 gm/kg per week with or without dexamethasone. Nonresponders after 4 to 6 weeks received continued intravenous gamma-globulin plus 60 mg of prednisone per day (\"salvage\").\n Dexamethasone did not add to the effect of intravenous gamma-globulin. Overall, there was a mean platelet increase from the first to the second fetal blood sampling of 36,000/microliters (n = 47) and from the first fetal blood sampling to birth of 69,000/microliters (n = 54). A total of 62% to 85% of fetuses responded. There were no intracranial hemorrhages. \"Salvage\" increased the platelet count in 5 of 10 nonresponders to intravenous gamma-globulin.\n Intravenous gamma-globulin treatment is appropriate for thrombocytopenic fetuses with alloimmune thrombocytopenia before use of weekly in utero platelet transfusions, even in severe thrombocytopenia.", "To determine the efficacy of antenatal low dose oral betamethasone in preventing neonatal thrombocytopenia and/or bleeding in infants of mothers with idiopathic thrombocytopenic purpura (ITP).\n Hospital department of obstetrics and gynaecology, referral centre.\n 41 pregnancies in 38 women were randomized. The results of 13 pregnancies were considered non-assessable. The final analysis involved 14 in the betamethasone group and 14 in the non-treatment group. All fulfilled the criteria for ITP.\n The treated group received 1.5 mg betamethasone orally per day, from day 259 till day 273 and 1 mg from day 273 till delivery.\n Effects of treatment were assessed in terms of maternal platelet counts after the first trimester and neonatal platelet counts at birth and the first week of life and neonatal bleeding episodes.\n There were no significant differences in neonatal platelet counts at birth. Two infants in the betamethasone group and one in the untreated group had a severe thrombocytopenia either at birth or during the first week of life (less than 50 x 10(9)/l). Seven infants in the betamethasone group and six in the non-treatment group had a mild thrombocytopenia. The overall frequency of neonatal thrombocytopenia was similar: 64% in the betamethasone group and 57% in the untreated group (95% CI of the true difference: -43.5% to +29.5%). There was also no significant difference in neonatal bleeding episodes.\n Low-dose betamethasone in pregnant women with ITP does not prevent thrombocytopenia or bleeding in their newborn infants.", "To determine whether adjunctive therapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival and to assess its safety compared with conventional therapy in a control group.\n This prospective, randomized, controlled trial was performed in 60 infants with neutropenia and clinical signs of sepsis. A subcutaneous injection of rhGM-CSF (5 microgram/kg/day) was administered to 30 of the patients for 7 consecutive days. Hematologic parameters (absolute neutrophil, eosinophil, monocyte, lymphocyte counts, and platelet number) and outcome were compared with 30 conventionally treated (control) patients.\n Twenty-five patients from the GM-CSF-treated group and 24 from the conventionally treated group had early-onset sepsis (</=3 days' postnatal age), and the other 11 patients had late-onset sepsis (>3 days' postnatal age). There was no difference between groups in terms of birth weight; gestational age; gender; maturity; maternal age; and incidence of prolonged rupture of membranes, maternal hypertension, or severity of sepsis. All neonates tolerated GM-CSF well with no adverse reactions. The absolute neutrophil count on day 7 was significantly increased in the GM-CSF-treated group compared with the conventionally treated group: 8088 +/- 2822/mm(3) versus 2757 +/- 823/mm(3). The mean platelet count was significantly higher on days 14 in the GM-CSF-treated group compared with conventionally treated group: 266 867 +/- 55 102/mm(3) versus 229 200 +/- 52 317/mm(3). Hematologic parameters were otherwise similar between groups before treatment and on day 28. Twenty-seven neonates in the rh-GMCSF group and 21 in the control group survived to hospital discharge. The mortality rate in the rhGM-CSF group (10%) was significantly lower than in the conventionally treated group (30%).\n Treatment with rhGM-CSF is associated with an increase in absolute neutrophil, eosinophil, monocyte, lymphocyte, and platelet counts and decreased mortality in critically ill septic neutropenic neonates. These results suggest that rhGM-CSF may be effective in the treatment of neonatal sepsis with neutropenia, and further randomized trials are needed to confirm its beneficial effects.", "The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy.\n Neonates (< or = 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of < or = 5 x 10(9)/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 microg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups.\n Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p < or = 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001).\n In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.", "To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL).\n Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval).\n CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups.\n G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.", "The purpose of this study was to conduct pilot studies for large randomized controlled trials to compare low-molecular-weight heparin with placebo for antenatal thromboprophylaxis (trial 1), and for thromboprophylaxis after cesarean delivery (trial 2).\n Multicenter randomized controlled trials (trial 1, 23 units; trial 2, 8 units) were conducted. Pregnant women at increased risk for thromboembolic disease were eligible for trial 1; women who underwent cesarean delivery were eligible for trial 2. The interventions were once daily injections of low-molecular-weight heparin or placebo. Primary outcomes were as follows: trial 1, confirmed symptomatic thromboembolic events and symptomatic osteoporotic fractures; trial 2, confirmed symptomatic thromboembolic events and wound complications.\n Sixteen women were recruited for trial 1; 1 woman in the placebo group had a symptomatic thromboembolic event. One hundred forty-one women were recruited for trial 2; 1 woman in the low molecular weight heparin group had a symptomatic thromboembolic event.\n Poor recruitment indicates that large-scale trials using these designs would be difficult. Collection of data on the number of women that are eligible and the reasons for nonrecruitment in future trials of these interventions would allow a better understanding of the reasons for poor recruitment.", "The addition of antithymocyte globulin (ATG) to a regimen of high-dose cyclophosphamide has been advocated to enhance engraftment after allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA). In a prospective clinical trial, 134 patients were randomly assigned to receive cyclophosphamide alone or in combination with ATG. All patients received T-cell-replete bone marrow from an HLA-matched sibling. With a median follow-up of 6 years, the 5-year probabilities of survival were 74% for the cyclophosphamide alone group and 80% for the cyclophosphamide plus ATG group (P = .44). Graft failure and graft-versus-host disease (GVHD) rates were similar in both groups. With the survival rates achieved, this study is not adequately powered to detect significant differences between the 2 treatment groups. In conclusion, the results of allogeneic BMT for SAA have improved over time related to advances in supportive care. The addition of ATG to the preparative regimen did not significantly improve the outcome." ]

[ "9190979", "12214830", "17466514", "15358335", "3595364", "1505264", "11862564", "8261970", "10330942" ]

[ "A randomized study comparing retroperitoneal drainage with no drainage after lymphadenectomy in gynecologic malignancies.", "A prospective randomized study comparing retroperitoneal drainage with no drainage and no peritonization following radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer.", "Randomised trial of drains versus no drains following radical hysterectomy and pelvic lymph node dissection: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group (EORTC-GCG) study in 234 patients.", "Gastric cancer surgery without drains: a prospective randomized trial.", "A prospective, controlled study of prophylactic drainage after colonic anastomoses.", "[Routine drainage following uncomplicated, elective cholecystectomy? A prospective, randomized study].", "A prospective randomised study of drains in infra-peritoneal rectal anastomoses.", "Cholecystectomy with and without drainage: a prospective randomised study.", "Is prophylactic pelvic drainage useful after elective rectal or anal anastomosis? A multicenter controlled randomized trial. French Association for Surgical Research." ]

[ "To evaluate the clinical effectiveness of retroperitoneal drainage following lymphadenectomy in gynecologic surgery.\n One hundred thirty-seven consecutive patients undergoing systematic lymphadenectomy for gynecologic malignancies were randomized to receive (Group A, 68) or not (Group B, 69) retroperitoneal drainage. The pelvic peritoneum and the paracolic gutters were not sutured after node dissection. Perioperative data and complications were recorded.\n Clinical and surgical parameters were comparable in the two groups. Postoperative hospital stay was significantly shorter in Group B (P < 0.001), whereas the complication rate was significantly higher in Group A (P = 0.01). This was mainly due to a significant increase in lymphocyst and lymphocyst-related morbidity. Sonographic monitoring for lymphocyst showed free abdominal fluid in 18% of drained and 36% of not-drained patients (P = 0.03). Symptomatic ascites developed in 2 drained (3%) and 3 not-drained (4%) patients (NS), respectively.\n Prophylactic drainage of the retroperitoneum seems to increase lymphadenectomy-related morbidity and postoperative stay. Therefore, routine drainage following lymphadenectomy seems to be no longer indicated when the retroperitoneum is left open.", "To evaluate the postoperative morbidity and lymphocyst formation in invasive cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (RHPL) with no drainage and no peritonization compared with retroperitoneal drainage and peritonization.\n Between July 1999 and May 2000, 100 patients with stage IA-IIA cervical cancer undergoing RHPL in Chiang Mai University Hospital were prospectively randomized to receive either no peritonization and no drainage (Group A = 48 cases) or retroperitoneal drainage and peritonization (Group B = 52 cases). Perioperative data and morbidity were recorded. Transabdominal and transvaginal sonography were performed at 4, 8 and 12 weeks postoperatively to detect lymphocyst formation.\n Both groups were similar regarding age, size and gross appearance of tumor, tumor histology and stage. There was no difference between groups in respect of operative time, need for blood transfusion, intraoperative complications, hospital stay, number of nodes removed, nodal metastases, and need for adjuvant radiation and chemotherapy. Asymptomatic lymphocysts were sonographically detected at 4, 8 and 12 weeks postoperatively in 3 (6.8%), 2 (4.6%), and 3 (7.7%) of 44, 43, and 39 patients, respectively in Group A, whereas none was found in Group B (P = 0.2). No significant difference was found in term of postoperative morbidity in the two groups.\n Routine retroperitoneal drainage and peritonization after RHPL for invasive cervical cancer can be safely omitted.", "Drainage, following radical hysterectomy and pelvic lymph node dissection to prevent postoperative lymphocyst formation and surgical morbidity, is controversial. To study the clinical significance of drainage, 253 patients were registered and 234 patients were randomised into two arms. In one arm (n=117) postoperative drainage was performed, in the other arm (n=117) no drains were inserted. In both arms closure of the peritoneum of the operating field was omitted. The main exclusion criteria were blood loss of more than 3000 ml during surgery or persistent oozing at the end of the operation. Clinical and ultrasound or CT-scan evaluation was done at one and 12 months postoperatively. The median follow-up amounted to 13.3 months. No difference in the incidence of postoperative lymphocyst formation or postoperative complications was found between the two study arms. The late (12 months) incidence of symptomatic lymphocysts was 3.4% (drains: 5.9%; no drains: 0.9%). The difference showed a p-value of 0.06 in Fisher's Exact test. The operating time was related to the occurrence of postoperative lymphocyst formation. It was concluded that drains can be safely omitted following radical hysterectomy and pelvic node dissection without pelvic reperitonisation in patients without excessive bleeding during or oozing at the end of surgery.", "Prophylactic drain placement during major abdominal surgery has been widely practiced without clear scientific evidence to support it. We hypothesized that prophylactic drain placement is not necessary in gastric cancer surgery. A randomized prospective trial was conducted between February 1, 2001, and July 30, 2001. Patients were randomly assigned to either the drain group or the no-drain group. One hundred seventy patients completed the study by undergoing either subtotal or total gastrectomy with D2 lymph node dissection. Surgical outcome between the two groups was compared within the subtotal and total gastrectomy subgroups. Postoperative complication within 30 days was the primary end point of the study. No significant difference was noted in the incidence of postoperative complication between the drain group and the no-drain group. The results of this study suggest that prophylactic drain placement does not offer additional benefit for patients undergoing gastric cancer surgery with extended lymph node dissection.", "A prospective, randomized, controlled trial was designed to study the influence of a corrugated latex drain on anastomotic integrity, wound infection, and respiratory complications after elective colonic resections above the pelvic peritoneum. Sixty patients entered the trial; 28 were drained and 32 undrained. Three patients in the undrained group died soon after surgery of causes unrelated to their colon anastomoses. There were no other differences in the incidence of postoperative complications in the two groups. When an anastomosis leaked, neither feces nor pus emerged via the drain. It is concluded that while the drains did not increase the incidence of postoperative complications, neither did they accomplish the purpose for which they were inserted. If, in addition, the economic cost of drainage is considered, it would seem that there is no advantage in inserting prophylactic drains after colonic anastomoses and their routine use needs to be reconsidered.", "A prospective randomized and controlled study of prophylactic drainage after simple, elective cholecystectomy was carried out. From March 1988 to June 1991 80 patients received an Easy-Flow drain and 80 did not. Operation and perioperative management were standardized. The endpoint of the study was postoperative morbidity, especially postoperative pyrexia and subhepatic fluid collection. The latter was identified by ultrasonography performed daily on postoperative day 1-4. No patient died. The morbidity including postoperative pyrexia revealed no difference between drained and undrained patients. In 19 of the patients with (23.8%) and in 25 of the patients without drainage (31.3%) a subhepatic fluid collection could be demonstrated by ultrasonography. This difference was not statistically significant either. We conclude that prophylactic drainage after elective, simple cholecystectomy is of no use for the patient. As subhepatic fluid collections can be seen in drained as well as in undrained patients it has to be accepted that drainage does not guarantee the removal of subhepatic fluid. Therefore its indicatory function (bleeding) and the ability to prevent the patient having biliary peritonitis or local abscess has to be put in doubt.", "Although increasing evidence suggests that prophylactic drainage after intra-peritoneal colorectal anastomoses is unnecessary, drains for infra-peritoneal rectal anastomoses, where the leak rate is higher, are widely employed still. The aim of this study was to assess the effect of prophylactic drainage after anastomosis below the peritoneal reflection. All patients attending one specialist unit over an 8-month period for elective rectal cancer resection with an infra-peritoneal anastomosis were randomised to drainage or no drainage. The incidence of anastomotic leak and complications specific to the drain as well as other complications were compared. Fifty-nine patients were analysed (31 with drain). Twenty-five of the drained and 16 of the no-drain patients had a defunctioning stoma (p=ns). The groups were comparable for demographic data, operation and anastomotic height from the anal verge. There were three leaks (10%) in the drain group and five leaks (18%) in the no-drain group (p=ns). There were 2 (7%) patients in each group with a clinical leak. There were no specific drain complications and the incidence of other complications was similar in both groups. In conclusion, this study supports the contention that there is no difference in morbidity with or without the use of a drain for infra-peritoneal anastomoses.", "The use of subhepatic intraperitoneal drains was prospectively studied in 100 patients who underwent elective cholecystectomy for symptomatic gallstones. These patients were randomised to have subhepatic drains (group A, n = 50 patients) or to have no drains (group B, n = 50 patients). There was no difference in the age or sex composition of the two groups. The patients were followed in the post-operative period (0-7 days) for evidence of fever, wound infection, septicaemia and any evidence of intra-peritoneal bile leakage. Also post operative hospital stay of patients was noted. In group A, 14 patients (28%) developed spikes of temperature of 38 degrees C or more while only 5 patients (10%) in group B developed such episodes. The difference was statistically significant between the two groups (P < 0.05). Wound infection occurred significantly more (P < 0.05) in group A (in 15 patients) as compared to group B (in 5 patients). Septicaemia occurred in 2 patients in group A and in none in group B. There was no evidence of intraperitoneal bile leakage in either group. Patients in group A tended to have longer post operative hospital stay (mean of 10.2 days) than patients in group B (mean 8.7 days); but the difference between the two groups in this respect was not significant. We conclude that subhepatic intra-peritoneal drains offered no additional advantage in elective cholecystectomy. The evidence we had pointed to their harmful effects.", "We investigated the role of drainage in the prevention of complications after elective rectal or anal anastomosis in the pelvis. Anastomotic leakage after colorectal resection is more prevalent when the anastomosis is in the distal or infraperitoneal pelvis than in the abdomen. The benefit of pelvic drains versus their potential harm has been questioned. Drain-related complications include (1) those possibly benefiting from drainage (leakage, intra-abdominal infection, bleeding) and (2) those possibly caused by drainage (wound infection or hernia, intestinal obstruction, fistula).\n Between September 1990 and June 1995, 494 patients (249 men and 245 women), mean age 66 +/- 15 (range 15 to 101) years, with either carcinoma, benign tumor, colonic Crohn's disease, diverticular disease of the sigmoid colon, or another disorder located anywhere from the right colon to the midrectum undergoing resection followed by rectal or anal anastomosis were randomized to undergo either drainage (n = 248) with 2 multiperforated 14F suction drains or no drainage (n = 246). The primary end point was the number of patients with one or more postoperative drain-related complications. Secondary end points included severity of these complications as assessed by the rate of related repeat operations and associated deaths as well as extra-abdominally related morbidity and mortality.\n After withdrawal of 2 patients (1 in each group) both groups were comparable with regard to preoperative characteristics and intraoperative findings. The overall leakage rate was 6.3% with no significant difference between those with or without drainage. There were 18 deaths (3.6%), 8 (3.2%) in those with drainage and 10 (4%) in those without drainage. Five patients with anastomotic leakage died (1%), 3 of whom had drainage. There were 32 repeat operations (6.5%) for anastomotic leakage 11 in the group with drainage and 4 in the group with no drainage. The rate of these and the other intra-abdominal and extra-abdominal complications did not differ significantly between the 2 groups.\n Prophylactic drainage of the pelvic space does not improve outcome or influence the severity of complications." ]

[ "14505443", "18454611", "19628939", "10990596", "17645384", "19442346", "17037953", "14669295", "16618375" ]

[ "The effects of music therapy on the quality and length of life of people diagnosed with terminal cancer.", "The effect of music therapy on anxiety in patients who are terminally ill.", "Effect of music therapy on anxiety and depression in patients with Alzheimer's type dementia: randomised, controlled study.", "The impact of music therapy on language functioning in dementia.", "Effects of music therapy on health-related outcomes in cardiac rehabilitation: a randomized controlled trial.", "Effects of a music therapy intervention on quality of life and distress in women with metastatic breast cancer.", "Use of preferred music to reduce emotional distress and symptom activity during radiation therapy.", "Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial.", "Music therapy in moderate and severe dementia of Alzheimer's type: a case-control study." ]

[ "The purpose of this study was to evaluate the effects of music therapy on quality of life, length of life in care, physical status, and relationship of death occurrence to the final music therapy interventions of hospice patients diagnosed with terminal cancer. Subjects were adults who were living in their homes, receiving hospice care, and were diagnosed with terminal cancer. A total of 80 subjects participated in the study and were randomly assigned to one of two groups: experimental (routine hospice services and clinical music therapy) and control (routine hospice services only). Groups were matched on the basis of gender and age. Quality of life was measured by the Hospice Quality of Life Index-Revised (HQOLI-R), a self-report measure given every visit. Functional status of the subjects was assessed by the hospice nurse during every visit using the Palliative Performance Scale. All subjects received at least two visits and quality of life and physical status assessments. A repeated measures ANOVA revealed a significant difference between groups on self-report quality of life scores for visits one and two. Quality of life was higher for those subjects receiving music therapy, and their quality of life increased over time as they received more music therapy sessions. Subjects in the control group, however, experienced a lower quality of life than those in the experimental group, and without music, their quality of life decreased over time. There were no significant differences in results by age or gender of subjects in either condition. Furthermore, there were no significant differences between groups on physical functioning, length of life, or time of death in relation to the last scheduled visit by the music therapist or counselor. This study provides an overview of hospice/palliative care, explains the role of music therapy in providing care, and establishes clinical guidelines grounded in research for the use of music therapy in improving the quality of life among the terminally ill.", "The literature supporting the use of music therapy in palliative care is growing. However, the number of quantitative research studies investigating the use of music therapy in palliative care, and specifically anxiety, is limited.\n The aim of this research project was to examine the effectiveness of a single music therapy session in reducing anxiety for terminally ill patients.\n A randomized-controlled design was implemented and the following hypotheses tested. There will be a significant difference between the experimental and control groups on anxiety levels as demonstrated by the anxiety measurement of the Edmonton Symptom Assessment System (ESAS), and heart rate. The experimental group received a single music therapy intervention and the control group received a volunteer visit.\n Twenty-five participants with end-stage terminal disease receiving inpatient hospice services were recruited.\n The first hypothesis was supported. Results demonstrated a significant reduction in anxiety for the experimental group on the anxiety measurement of the ESAS (p = 0.005). A post hoc analysis found significant reductions in other measurements on the ESAS in the experimental group, specifically pain (p = 0.019), tiredness (p = 0.024) and drowsiness (p = 0.018). The second hypothesis was not supported.\n The study supports the use of music therapy to manage anxiety in terminally ill patients. Further studies are required to examine the effect of music therapy over a longer time period, as well as addressing other symptom issues.", "Numerous studies have indicated the value of music therapy in the management of patients with Alzheimer's disease. A recent pilot study demonstrated the feasibility and usefulness of a new music therapy technique. The aim of this controlled, randomised study was to assess the effects of this new music therapy technique on anxiety and depression in patients with mild to moderate Alzheimer-type dementia.\n This was a single-centre, comparative, controlled, randomised study, with blinded assessment of its results. The duration of follow-up was 24 weeks. The treated group (n = 15) participated in weekly sessions of individual, receptive music therapy. The musical style of the session was chosen by the patient. The validated 'U' technique was employed. The control group (n = 15) participated under the same conditions in reading sessions. The principal endpoint, measured at weeks 1, 4, 8, 16 and 24, was the level of anxiety (Hamilton Scale). Changes in the depression score (Geriatric Depression Scale) were also analyzed as a secondary endpoint.\n Significant improvements in anxiety (p < 0.01) and depression (p < 0.01) were observed in the music therapy group as from week 4 and until week 16. The effect of music therapy was sustained for up to 8 weeks after the discontinuation of sessions between weeks 16 and 24 (p < 0.01).\n These results confirm the valuable effect of music therapy on anxiety and depression in patients with mild to moderate Alzheimer's disease. This new music therapy technique is simple to implement and can easily be integrated in a multidisciplinary programme for the management of Alzheimer's disease.\n Copyright 2009 S. Karger AG, Basel.", "Dementias, such as Alzheimer's disease, include a progressive deterioration of language functioning. While some researchers have reported an increase in patients' self-expression following music therapy, it is not clear whether these changes specifically reflect improved language skills or whether simple interpersonal interaction with a therapist could account for the improvement. In this study, the effects of music therapy were compared to conversational sessions on language functioning in dementia patients. Participants were selected according to the following criteria: (a) residing in a facility specializing in Alzheimer's and related disorders; (b) possessing sufficient verbal ability to answer simple questions and to comply with requests to speak, participate, or sit down; and (c) attaining the written consent of the patient's guardian or representative. All participants had been in music therapy twice per week for at least 3 months prior to the study onset. One week prior to the beginning of the study, subjects were assessed for cognitive functioning using the Mini-Mental State Examination (MMSE), and language ability via the Western Aphasia Battery (WAB). A within-subjects design was used, with order of condition (music or group conversation first) counter-balanced between participants. Subjects participated in groups of 2 to 4, twice per week for 20-30 minutes for a total of 8 sessions (4 music therapy and 4 conversation sessions or vice-versa), and were re-tested on the WAB at the end of each 2 week (4 session) interval. Results from 20 participants revealed that music therapy significantly improved performance on both speech content and fluency dimensions of the spontaneous speech subscale of the WAB (p =.01). While the difference in overall Aphasia Quotient (AQ) for music and conversation sessions (mean AQ = 76 vs. 70, respectively) did not reach statistical significance, data were only available for 10 participants (5 per condition). Hopefully, these findings will stimulate additional research on the use of music therapy interventions with demented patients, as it may offer a noninvasive mechanism to enhance communication between victims and their caregivers.", "This study tested effectiveness of music therapy in improving health-related outcomes of cardiac rehabilitation patients. Using a randomized, controlled trial with follow-up, the study was conducted in an outpatient cardiac rehabilitation program in Ohio. Sixty-eight of 103 recruited patients, 30 to 80 years of age, completed the protocol through posttreatment. Physiological and psychological outcomes were measured. Cardiac rehabilitation patients were randomly assigned to cardiac rehabilitation only or to music therapy plus cardiac rehabilitation. Music therapy included musical experiences, counseling, and Music-Assisted Relaxation and Imagery. The null hypothesis of no differences in health-related outcomes between cardiac rehabilitation patients who experienced cardiac rehabilitation with and without music therapy was rejected due to changes in systolic blood pressure pre to post-treatment. Interpretation of changes at 4 months posttreatment in anxiety, general health, and social functioning are limited, due to small sample sizes at follow-up. Pre to post-music therapy session improvements were also reported. Findings suggest that some health-related outcomes may be affected positively by participation in music therapy in addition to cardiac rehabilitation. Attrition contributed to limitations in statistical power.", "This study examined the effects of music therapy (MT), immediate and over time, on patients' psychological functioning, quality of life, and physiologic stress arousal. This intervention, whereby patients use music strategies to cope with cancer-related stressors, is based on a transactional stress-coping framework. Using a longitudinal, randomized controlled design, 70 women with metastatic breast cancer received either MT or usual care. The MT consisted of three individual sessions led by a music therapist. Psychological symptoms were measured with the Hospital Anxiety and Depression Scale and quality of life with the Functional Assessment of Cancer Therapy-General plus a a Spirituality subscale at baseline approximately 6 weeks and 3 months later. Visual analog scales, heart rate, and blood pressure were assessed in the MT group immediately before and after individual session. Significant immediate effects of MT were observed: relaxation, p = < .00001; comfort, p = < . 00001; happiness, p = < .00001; heart rate, p = .0003; although no significant differences between conditions were found over time. A high attrition rate underscored the complexities inherent in conducting intervention research with advanced cancer patients.", "Music therapy has decreased anxiety levels in many medical settings. This randomized clinical trial examined the effectiveness of a music listening intervention, delivered by a board-certified music therapist, in patients undergoing curative radiation therapy (RT). Emotional distress (anxiety, depression, and treatment-related distress) and symptoms (fatigue and pain) were measured at baseline, mid-treatment, and end of treatment in 63 patients undergoing RT. Although patients who listened to self-selected music reported lower anxiety and treatment-related distress, there was a decline in these outcomes for patients in both groups over the course of RT. Depression, fatigue, and pain were not appreciably affected by music therapy. Within the music group, there was a significant correlation between number of times music was used/week and the change in treatment-related distress, suggesting that higher doses of music produced greater declines in distress. While these findings provided some support for the use of music in reducing distress during RT, further research demonstrating clear differences between intervention and control conditions is needed. Physical symptoms were not affected by the use of music over the course of RT.", "High-dose therapy with autologous stem cell transplantation (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The procedure causes significant psychological distress and no interventions have been demonstrated to improve mood in these patients. Music therapy has been shown to improve anxiety in a variety of acute medical settings. In the current study, the authors determined the effects of music therapy compared with standard care on mood during inpatient stays for HDT/ASCT.\n Patients with hematologic malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive music therapy given by trained music therapists or standard care. Outcome was assessed at baseline and every 3 days after randomization using the Profile of Mood States.\n Of 69 patients registered in the study, follow-up data were available for 62 (90%). During their inpatient stay, patients in the music therapy group scored 28% lower on the combined Anxiety/Depression scale (P = 0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with controls.\n Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT.\n Copyright 2003 American Cancer Society.", "Music therapy is a potential non-pharmacological treatment for the behavioral and psychological symptoms of dementia, but although some studies have found it to be helpful, most are small and uncontrolled.\n This case-control study was carried out by qualified music therapists in two nursing homes and two psychogeriatric wards. The participants were 38 patients with moderate or severe Alzheimer's disease (AD) assigned randomly to a music therapy group and a control group.\n The study showed a significant reduction in activity disturbances in the music therapy group during a 6-week period measured with the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). There was also a significant reduction in the sum of scores of activity disturbances, aggressiveness and anxiety. Other symptoms rated by subscales of the BEHAVE-AD did not decrease significantly. Four weeks later the effects had mostly disappeared.\n Music therapy is a safe and effective method for treating agitation and anxiety in moderately severe and severe AD. This is in line with the results of some non-controlled studies on music therapy in dementia." ]

[ "3045281", "19797281", "323443", "9506654", "3534201", "10201714", "363995", "6516811", "20855387" ]

[ "Clinical trial of naloxone in birth asphyxia.", "Moderate hypothermia to treat perinatal asphyxial encephalopathy.", "Use of nalotone to to reverse narcotic respiratory depression in the newborn infant.", "High-dose phenobarbital therapy in term newborn infants with severe perinatal asphyxia: a randomized, prospective study with three-year follow-up.", "Use of barbiturate therapy in severe perinatal asphyxia: a randomized controlled trial.", "Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates.", "Naloxone reversal of mild neurobehavioral depression in normal newborn infants after routine obstetric analgesia.", "Effects of naloxone on newborn infant behavior after maternal analgesia with pethidine during labor.", "Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT." ]

[ "To determine whether endogenous opiates play a role in the pathogenesis of perinatal asphyxia, a blinded clinical trial of naloxone, a competitive opiate receptor blocker, was undertaken in infants with low 1-minute Apgar scores. Of 85 infants with 1-minute Apgar score 0 to 3, 44 received an injection of naloxone (approximately 0.4 mg/kg) and 41 received saline solution. In 108 infants with 1-minute Apgar score 4 to 6, 54 received naloxone and 54 saline solution. In neither group was there a significant effect of naloxone on respiratory frequency or heart rate up to 30 minutes after injection, nor at 24 hours of age. In both groups active muscle tone of upper and lower limbs was increased by naloxone, a response that may not be beneficial in the face of inadequate oxygen delivery to vital organs. We conclude that naloxone at this dose had no readily apparent benefit in the resuscitation of the asphyxiated newborn infant.", "Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.\n We performed a randomized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy. We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone. The primary outcome was death or severe disability at 18 months of age. Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes.\n Of 325 infants enrolled, 163 underwent intensive care with cooling, and 162 underwent intensive care alone. In the cooled group, 42 infants died and 32 survived but had severe neurodevelopmental disability, whereas in the noncooled group, 44 infants died and 42 had severe disability (relative risk for either outcome, 0.86; 95% confidence interval [CI], 0.68 to 1.07; P=0.17). Infants in the cooled group had an increased rate of survival without neurologic abnormality (relative risk, 1.57; 95% CI, 1.16 to 2.12; P=0.003). Among survivors, cooling resulted in reduced risks of cerebral palsy (relative risk, 0.67; 95% CI, 0.47 to 0.96; P=0.03) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II (P=0.03 for each) and the Gross Motor Function Classification System (P=0.01). Improvements in other neurologic outcomes in the cooled group were not significant. Adverse events were mostly minor and not associated with cooling.\n Induction of moderate hypothermia for 72 hours in infants who had perinatal asphyxia did not significantly reduce the combined rate of death or severe disability but resulted in improved neurologic outcomes in survivors. (Current Controlled Trials number, ISRCTN89547571.)\n 2009 Massachusetts Medical Society", "Twenty neonates whose mothers had received meperidine (1.0 to 1.5 mg/kg) intravenously within three hours of delivery were studied to determine the effectiveness of naloxone in reversing neonatal respiratory depression. The following measurements were carried out within 20 to 30 minutes after delivery: minute ventilation, end tidal CO2, and ventilatory response to CO2. These determinations were repeated after administration of either placebo or naloxone, 0.01 mg/kg intramuscularly. Minute ventilation and PAco were within a normal range before medication in both groups, but the slope of the CO2 response curve was decreased, indicating mild-to-moderate respiratory depression. After administration of placebo the test results did not change significantly. After administration of naloxone, VE increased significantly (P less than 0.05) and the slope of the CO2 response curve doubled (P less than 0.001). Naloxone effectively reverses narcotic depression of the respiratory center in the newborn infant.", "To determine whether 40 mg/kg phenobarbital given to term infants with severe asphyxia would result in a lower incidence of seizures in the newborn period and an improved neurologic outcome.\n We conducted a randomized, controlled, prospective study. Entry criteria included (1) an initial arterial pH less than or equal to 7.0 with a base deficit 15 mEq/L or more, (2) Apgar score less than or equal to 3 at 5 minutes of age, or (3) failure to initiate spontaneous respiration by 10 minutes of age. Sample size was calculated to detect a 50% reduction in the incidence of neonatal seizures.\n No differences were present between treatment and control groups with respect to severity of asphyxia assessed by initial arterial pH, base excess, cerebrospinal fluid lactate dehydrogenase concentration or detection of CSF creatine kinase of its BB isoenzyme. Seizures occurred in 9 of 15 infants in the treatment group and 14 of 16 infants in the control group (p = 0.11). No adverse effects were observed from phenobarbital on heart rate, respiratory rate, blood pressure, or arterial blood gas values. Three-year follow-up revealed normal outcome in 11 of 15 infants in the treatment group and 3 of 16 in the control group (p = 0.003).\n Phenobarbital, when administered in a dose of 40 mg/kg intravenously over 1 hour in term, severely asphyxiated newborn infants appeared to be safe and was associated with a 27% reduction in the incidence of seizures and a significant improvement in neurologic outcome at 3 years of age.", "The possible cerebral sparing effect of thiopental was evaluated in 32 severely asphyxiated neonates randomly assigned to either a thiopental treatment or control group. All infants had neurologic manifestations of asphyxia and required assisted ventilation. Thiopental was begun at a mean age of 2.3 hours and was given as a constant infusion that delivered 30 mg/kg over 2 hours. Treatment was continued at a lower dose for 24 hours. Seizure activity occurred in 76% of infants given thiopental and 73% of control infants at a mean age of 1.5 and 2.5 hours, respectively. Although initial arterial blood pressure was similar in both groups, hypotension occurred in 88% of treated and 60% of control infants. The amount of blood pressure support required was significantly greater (P less than 0.005) in the thiopental treatment group. Three infants died in the control group, and five in the treatment group. Developmental assessment was performed at a minimum of 12 months of age in 22 infants. There were no significant differences in neurologic, cognitive, or motor outcome between groups. Deteriorating performance over time was a consistent trend in both groups. These findings indicate that treatment of severe perinatal asphyxia with thiopental does not appear to have a cerebral sparing effect and may be associated with significant arterial hypotension.", "Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo.\n To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis.\n Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia.\n No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group.\n This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial.", "To investigate the presence of subtle narcotic depression following maternal narcotic analgesia, we have evaluated the effects of naloxone versus placebo in a double-blind parallel group study in 43 normal term newborn infants whose mothers had received routine narcotic analgesia within six hours prior to delivery. Infants were given either an intramuscular injection of 20 microgram/kg naloxone or 0.20 ml/kg placebo after determination of the one-minute Apgar score, and the following measurements were compared: Apgar scores at one and five minutes, capillary blood gas values at one, 60, 120, and 240 minutes, and neurobehavioral assessments at one, 4, and 24 hours. No adverse effects from naloxone were observed. Neither Apgar scores nor capillary blood gas determinations differed significantly between the two groups. Response to sound was significantly higher in the naloxone group at 24 hours. The alertness score was significantly higher for the naloxone group at one and four hours; the general assessment score for the naloxone group was significantly higher at four and 24 hours. Average scores of naloxone and placebo groups were also different at four and 24 hours of age. These data demonstrate that maternal narcotic analgesia may produce subtle changes in alertness and general behavior not reflected by Apgar scores or respiratory status, potentially reversible by administration of naloxone shortly following delivery.", "Infants born to mothers receiving 100 mg of pethidine during labor, were randomly given either 100 micrograms of naloxone (n = 14) or 0.25 ml 0.9% NaCl (n = 13) one hour post partum. Infant behavior was assessed with the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) and the Broussard Neonatal Perception Inventory (NPI). No differences in cluster scores on the BNBAS were found between the two groups. Both groups improved scores over time in 4 out of 7 clusters. On the NPI, mothers assessed naloxone infants as having less optimal behavior than did the control mothers. The results of this study on the effects of naloxone on infant behavior and maternal perception of newborn behavior do not warrant administration of naloxone after maternal analgesia with pethidine in the absence of clinical evidence of respiratory depression in the newborn.", "Mild hypothermia after perinatal hypoxic-ischemic encephalopathy (HIE) reduces neurologic sequelae without significant adverse effects, but studies are needed to determine the most-efficacious methods.\n In the neo.nEURO.network trial, term neonates with clinical and electrophysiological evidence of HIE were assigned randomly to either a control group, with a rectal temperature of 37°C (range: 36.5-37.5°C), or a hypothermia group, cooled and maintained at a rectal temperature of 33.5°C (range: 33-34°C) with a cooling blanket for 72 hours, followed by slow rewarming. All infants received morphine (0.1 mg/kg) every 4 hours or an equivalent dose of fentanyl. Neurodevelopmental outcomes were assessed at the age of 18 to 21 months. The primary outcome was death or severe disability.\n A total of 129 newborn infants were enrolled, and 111 infants were evaluated at 18 to 21 months (53 in the hypothermia group and 58 in the normothermia group). The rates of death or severe disability were 51% in the hypothermia group and 83% in the normothermia group (P=.001; odds ratio: 0.21 [95% confidence interval [CI]: 0.09-0.54]; number needed to treat: 4 [95% CI: 3-9]). Hypothermia also had a statistically significant protective effect in the group with severe HIE (n=77; P=.005; odds ratio: 0.17 [95% CI: 0.05-0.57]). Rates of adverse events during the intervention were similar in the 2 groups except for fewer clinical seizures in the hypothermia group.\n Systemic hypothermia in the neo.nEURO.network trial showed a strong neuroprotective effect and was effective in the severe HIE group." ]

[ "19457937", "17290061", "17822748", "20619634", "16868539", "17237853", "11063636", "17996926", "16330675" ]

[ "Randomized multicenter phase II trial of cisplatin and ifosfamide with or without paclitaxel in recurrent or metastatic carcinoma of the uterine cervix: a Hellenic Cooperative Oncology Group (HeCOG) study.", "Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study.", "A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus.", "Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies.", "Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial.", "Randomized study of concurrent carboplatin, paclitaxel, and radiotherapy with or without prior induction chemotherapy in patients with locally advanced non-small cell lung cancer.", "A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study.", "Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study.", "Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study." ]

[ "We undertook a randomized phase II trial to test whether the addition of paclitaxel (Taxol) to the cisplatin and ifosfamide (IP) combination could improve objective response (OR) rate, progression-free survival (PFS) and overall survival (OS) in patients with recurrent or metastatic cancer of the uterine cervix.\n One hundred and fifty-three patients were randomly allocated to receive either the IP regimen (ifosfamide 1.5 g/m(2), daily, on days 1-3 and cisplatin 70 mg/m(2) on day 2) or the same combination with the addition of paclitaxel 175 mg/m(2) on day 1 [ifosfamide, paclitaxel and cisplatinum (ITP) regimen]. Cycles were administered every 4 weeks on an outpatient basis.\n A modest increase in neurotoxicity was observed with the triplet combination. OR rate was significantly higher in the ITP group (59% versus 33%, P = 0.002). Median PFS was 7.9 and 6.3 months for patients in the ITP and IP arms, respectively (P = 0.023). Median OS was 15.4 months and 13.2 months in the ITP and IP arms, respectively (P = 0.048). In multivariate analysis, the triplet yielded a hazard ratio of 0.70 for relapse or progression (P = 0.046) and 0.75 for death (P = 0.124) compared with the doublet.\n The ITP combination merits further investigation in randomized phase III studies.", "To determine if paclitaxel added to ifosfamide as first-line treatment for advanced uterine carcinosarcoma (CS) improves overall survival (OS), progression-free survival (PFS), response, and toxicity.\n Eligible patients had measurable stage III or IV, persistent, or recurrent uterine CS. Random assignment to treatment was between ifosfamide 2.0 g/m2 intravenously (IV) daily for 3 days (arm 1) or ifosfamide 1.6 g/m2 IV daily for 3 days plus paclitaxel 135 mg/m2 by 3-hour infusion day 1 (arm 2). Mesna was administered similarly (both arms); filgrastim began on day 4 (arm 2). Cycles were repeated every 21 days up to eight cycles.\n Of 214 patients enrolled, 179 were eligible (arm 1, 91 patients; arm 2, 88 patients). Arm 2 patients experienced more frequent and severe sensory neuropathy (grade 1 to 4; 8% v 30%). The crude response rate was 29% (arm 1) and 45% (arm 2). The odds of response stratified by performance status were 2.21 greater in arm 2 (P = .017). Median PFS and OS, respectively, for arm 1 compared with arm 2 were 3.6 v 5.8 months and 8.4 v 13.5 months, respectively. There was a 31% decrease in the hazard of death (hazard ratio [HR], 0.69; 95% CI, 0.49 to 0.97; P = .03) and a 29% decrease in the hazard of progression (HR, 0.71; 95% CI, 0.51 to 0.97; P = .03) relative to arm 1 when stratifying by performance status.\n OS was significantly improved in arm 2, and toxicities were as expected and manageable. However, the need for active new agents persists, given that OS remains relatively poor in this disease.", "After initial surgery, there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma (CS). This study was designed to compare patient outcome following treatment with adjuvant whole abdominal irradiation (WAI) versus (vs.) chemotherapy for patients with this rare group of female pelvic malignancies.\n Eligible, consenting women with stage I-IV uterine CS, no more than 1 cm postsurgical residuum and/or no extra-abdominal spread had their treatments randomly assigned as either WAI or three cycles of cisplatin (C), ifosfamide (I), and mesna (M).\n 232 patients were enrolled, of whom 206 (WAI=105; CIM=101) were deemed eligible. Patient demographics and characteristics were similar between arms. FIGO stage (both arms) was: I=64 (31%); II=26 (13%); III=92 (45%); IV=24 (12%). The estimated crude probability of recurring within 5 years was 58% (WAI) and 52% (CIM). Adjusting for stage and age, the recurrence rate was 21% lower for CIM patients than for WAI patients (relative hazard [RH]=0.789, 95% confidence interval [CI]: (0.530-1.176), p=0.245, 2-tail test). The estimated death rate was 29% lower among the CIM group (RH=0.712, 95% CI: 0.484-1.048, p=0.085, two-tail test).\n We did not find a statistically significant advantage in recurrence rate or survival for adjuvant CIM over WAI in patients with uterine CS. However, the observed differences favor the use of combination chemotherapy in future trials.", "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.", "Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m(-2)), doxorubicin (45 mg m(-2)), cyclophosphamide (600 mg m(-2)) every 28 days for five cycles, or external RT (45-50 Gy on a 5 days week(-1) schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66-1.36; P = 0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63-1.23; P = 0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited.", "Multiple concepts of combined modality therapy for locally advanced inoperable non-small cell lung cancer have been investigated. These include induction chemotherapy, concomitant chemo-radiotherapy, and radiation only. To date, combined modality therapy specially the use of concomitant chemo-radiotherapy has led to promising results and was shown to be superior to radiotherapy alone in phase II studies. However the optimum chemo-therapeutic regimen to be used as well as the benefit of induction chemotherapy before concomitant chemo-radiotherapy are yet to be determined. Based on these observations, we investigated the use of paclitaxel and carboplatin concomitantly with radiotherapy and the benefit of prior two cycles induction chemotherapy.\n In this trial 60 patients with locally advanced inoperable non small cell lung cancer, good performance status and minimal weight loss have been randomized into 3 groups each of 20 patients. Group A received induction 2 cycles paclitaxel (175 mg/m2) and carboplatin (AUC 6) on day 1 and 28th followed by concomitant paclitaxel (45 mg/m2) and carboplatin (AUC 2) weekly with radiotherapy. Group B received concomitant carboplatin, paclitaxel (same doses as in group A) and radiotherapy with no prior induction chemotherapy. Group C received only radiotherapy to a total dose of 60 Gy in conventional fractionation.\n A total of 60 patients were enrolled in this study between 1998 and 2000. Pretreatment characteristics, including age, gender, performance status, histological features and stage were comparable in each group. The incidence of oesophagitis was significantly higher in group A and B than in group C (p=0.023). Hematological toxicities was also significantly higher in group A & B than in group C (p=0.003). The response rate was significantly higher in group A and B than in group C (75%, 79%, and 40% respectively) (p=0.020). The time to in-field progression was significantly higher in group B as compared to group A (48% vs. 32% failure in 2 years respectively) (p=0.000). The median 2 year survival was significantly higher in group A and B than in group C (p=0.039) but no statistical difference was seen between group A and B.\n Combined chemo-radiotherapy resulted in better response and survival as compared to conventional radiotherapy in the treatment of locally advanced nonsmall cell lung cancer. Early initiation of radiation with concomitant chemotherapy resulted in prolonged time to infield progression. On the other hand, two cycles of induction chemotherapy did not show any significant difference regarding the response or survival. Weekly paclitaxel and carboplatin plus radiotherapy is a well tolerated regimen for outpatients with encouraging results.", "The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population.\n Patients were randomized to receive ifosfamide (1.5 g/m(2)/day) times 5 days every 3 weeks for eight courses with mesna uroprotection, with or without cisplatin (20 mg/m(2)/day) times 5 days. No patient had received previous chemotherapy.\n Of 224 patients entered on this study, 30 were ineligible for a variety of reasons, leaving 194 evaluable patients. Early in the study, the dose of the combination regimen was reduced by 20% (1 day) because of toxicity. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosfamide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), grade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 peripheral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. The proportion of patients responding to ifosfamide alone versus ifosfamide-cisplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvic, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for \"other\" metastatic sites of measurable disease. The relative odds ratio of response adjusted for measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lower confidence limit, 1.06). Progression-free survival (PFS) and survival data suggest that the combination offers a slight prolongation of PFS (relative risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confidence limit, 1.03; P = 0.071, one-tailed test).\n The addition of cisplatin to ifosfamide appears to offer a small improvement in progression-free survival over ifosfamide alone in the management of advanced carcinosarcoma of the uterus; the added toxicity may not justify the use of this combination.\n Copyright 2000 Academic Press.", "To establish an optimal adjuvant therapy for intermediate- and high-risk endometrial cancer patients, we conducted a multi-center randomized phase III trial of adjuvant pelvic radiation therapy (PRT) versus cyclophosphamide-doxorubicin-cisplatin (CAP) chemotherapy in women with endometrioid adenocarcinoma with deeper than 50% myometrial invasion.\n Among 385 evaluated patients, 193 patients received PRT and 192 received CAP. The PRT group received at least 40 Gy. The CAP group received cyclophosphamide (333 mg/m2), doxorubicin (40 mg/m2) and cisplatin (50 mg/m2) every 4 weeks for 3 or more courses.\n No statistically significant differences in progression-free survival (PFS) and overall survival (OS) were observed. The 5-year PFS rates in the PRT and CAP groups were 83.5% and 81.8% respectively, while the 5-year OS rates were 85.3% and 86.7% respectively. These rates were also not significantly different in a low- to intermediate-risk group defined as stage IC patients under 70 years old with G1/2 endometrioid adenocarcinoma. However, among 120 patients in a high- to intermediate-risk group defined as (1) stage IC in patients over 70 years old or with G3 endometrioid adenocarcinoma or (2) stage II or IIIA (positive cytology), the CAP group had a significantly higher PFS rate (83.8% vs. 66.2%, log-rank test P=0.024, hazard ratio 0.44) and higher OS rate (89.7% vs. 73.6%, log-rank test P=0.006, hazard ratio 0.24). Adverse effects were not significantly increased in the CAP group versus the PRT group.\n Adjuvant chemotherapy may be a useful alternative to radiotherapy for intermediate-risk endometrial cancer.", "To compare whole-abdominal irradiation (WAI) and doxorubicin-cisplatin (AP) chemotherapy in women with stage III or IV endometrial carcinoma having a maximum of 2 cm of postoperative residual disease.\n Four hundred twenty-two patients were entered onto this trial. Of 396 assessable patients, 202 were randomly allocated to receive WAI, and 194 were allocated to receive AP. Irradiation dosage was 30 Gy in 20 fractions, with a 15-Gy boost. Chemotherapy consisted of doxorubicin 60 mg/m2 and cisplatin 50 mg/m2 every 3 weeks for seven cycles, followed by one cycle of cisplatin.\n Most patient and tumor characteristics were well balanced. The median patient age was 63 years; 50% had endometrioid tumors. Median follow-up time was 74 months. The hazard ratio for progression adjusted for stage was 0.71 favoring AP (95% CI, 0.55 to 0.91; P < .01). At 60 months, 50% of patients receiving AP were predicted to be alive and disease free when adjusting for stage compared with 38% of patients receiving WAI. The stage-adjusted death hazard ratio was 0.68 (95% CI, 0.52 to 0.89; P < .01) favoring AP. Moreover, at 60 months and adjusting for stage, 55% of AP patients were predicted to be alive compared with 42% of WAI patients. Greater acute toxicity was seen with AP. Treatment probably contributed to the deaths of eight patients (4%) on the AP arm and five patients (2%) on the WAI arm.\n Chemotherapy with AP significantly improved progression-free and overall survival compared with WAI. Nevertheless, further advances in efficacy and reduction in toxicity are clearly needed." ]

[ "15760929", "11561117", "14552308", "16926184", "1642652", "17235556", "17485422", "2919941", "13130460" ]

[ "A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs.", "One-year outcomes of a randomized controlled trial of an educational-behavioural joint protection programme for people with rheumatoid arthritis.", "Auranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study.", "Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study.", "Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial.", "Preliminary evaluation in rheumatoid arthritis activity in patients treated with TNF-alpha blocker plus methotrexate versus methotrexate or leflunomide alone.", "Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab.", "Toxicity of methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. A case-control study of 131 patients.", "Is a long-term high-intensity exercise program effective and safe in patients with rheumatoid arthritis? Results of a randomized controlled trial." ]

[ "In rheumatoid arthritis (RA), intramuscular (IM) pulsed depomedrone expedites an immediate response to disease modifying antirheumatic drugs (DMARDs). Although IM depomedrone is also widely used to treat disease flares in patients treated with DMARDs, its effect on radiological progression has not been assessed.\n To evaluate the benefits of 120 mg IM depomedrone versus placebo in patients with established RA whose disease was inadequately controlled by existing DMARDs.\n In a 2 year prospective randomised controlled trial patients were assessed using the ILAR/WHO core dataset, disease activity score (DAS28), x ray examination of hands and feet scored by Larsen's method, and bone densitometry.\n 291 patients with RA were screened, 166 were eligible, and 91 consented and were randomised. Disease activity improved more rapidly in the steroid treated patients than with placebo, but after 6 months no difference remained. A small but significant reduction in erosive damage in the steroid group compared with placebo was also found. More adverse reactions occurred in the steroid treated group than in the placebo patients (55 v 42), especially those reactions traditionally related to steroids (16 v 2), including vertebral fracture, diabetes, and myocardial infarction. Hip bone density fell significantly in steroid treated but not placebo patients.\n IM depomedrone improved disease activity in the short term and produced a small reduction in bone erosion at the cost of a significant increase in adverse events. Despite the initial benefit of IM depomedrone, when patients respond suboptimally to a DMARD they should not be given long term additional steroids but should be treated with alternative or additional DMARDs.", "Joint protection aims to reduce pain and local inflammation, preserve the integrity of joint structures and improve function. There is evidence that it can improve pain and function in the short term, but the long-term effects are uncertain. This study evaluated the effects of joint protection in early rheumatoid arthritis (RA).\n A randomized, controlled, assessor-blinded trial of duration 1 yr was conducted. Two interventions (both 8 h) were compared: standard arthritis education, including 2.5 h of joint protection education based on typical UK practice; and a joint protection arthritis education programme, using educational-behavioural teaching methods. Assessments were made at entry and 6 and 12 months.\n Sixty-five people with RA attended the joint protection programme and 62 the standard programme. The groups were matched for age (51 and 49 yr), disease duration (21 and 17.5 months) and use of non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs. In comparison with the standard group, the joint protection group significantly improved with respect to adherence to the joint protection programme (P=0.001), hand pain (P=0.02), general pain (P=0.05), early morning stiffness (P=0.01), self-reported number of disease flare-ups (P=0.004), visits to the doctor for arthritis (P<0.01), and the AIMS2 (Arthritis Impact Measurement Scales) activities of daily living scale (P=0.04). A trend to improved swollen joint counts was identified (P=0.07). Within-group analyses also showed improvements in arthritis self-efficacy and perceived control. Hand deformity scores continued to increase in both groups.\n We found significant improvements in adherence, pain, disease status and functional ability amongst those attending the joint protection programme. Benefits became more apparent with time, suggesting that joint protection can help slow the progression of the effects of RA over and above the effects of drug therapy.", "The effect of early initiation of auranofin (AF) therapy on outcome measures was studied in a controlled 24-month double blind trial in 138 patients with early rheumatoid arthritis (RA) using an intent to treat approach. Patients were randomized to AF or placebo but in case of insufficient effect or intolerable adverse events, they switched to open disease modifying antirheumatic drug therapy. Patients who started AF fared significantly better in improved joint swelling. Stanford Health Assessment Questionnaire index, Keitel functional test, and mental depression, and furthermore, radiologic progression was significantly retarded. Our results support a disease modifying beneficial effect of AF in early active RA.se", "Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. Aim: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP.\n A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) > or =2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS.\n At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy.\n In this \"true-to-life\" study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies.", "To compare the relative safety and efficacy of azathioprine (AZA), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA).\n Two hundred twelve patients with active RA were entered into a 24-week prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups.\n One hundred fifty-eight patients finished 24 weeks of the study. There were no remissions seen but response rates were greater than 30% for all outcome measures. Combination therapy was not statistically superior to MTX therapy alone, but both combination therapy and MTX alone were superior to AZA alone when patients were analyzed by intent-to-treat and with withdrawals treated as therapy failures. If only patients who continued taking the therapy were analyzed, the mean improvement was greater for AZA therapy than for MTX, while the combination remained the most active. Adverse effects on the gastrointestinal tract and elevations of liver enzyme levels were the most frequent causes for discontinuations.\n Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment.", "Methotrexate (MTX) is a first-line disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA). Leflunomide (LEF) and the biologic agents entered the arsenal of DMARDs in 1998. Therapeutic properties of new drugs are still under survey. The purpose of this study was to evaluate and compare the efficacy of MTX, LEF and a biologic agent (TNF-alpha blocker) combined with MTX in reducing disease activity in RA. Seventy-eight patients with active RA underwent a 24-week treatment with MTX 15 mg/week (30 pts), LEF 20 mg/day (30 pts) or a TNF-alpha blocker (etanercept 25 mg 2x weekly or infliximab 3 mg/kg in the week 0, 2, 6 and every 8 weeks thereafter) plus MTX 15 mg/week (18 pts). Only patients with RA resistant to MTX were included in groups receiving LEF or a biologic agent. During follow-up, patients' characteristics, disease characteristics, and clinical and laboratory data were registered. RA activity was evaluated using the ESR, tender and swollen joint counts, the duration of morning stiffness, disease activity score-28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment efficacy was demonstrated with ACR 20, 50 and 70 criteria. All groups revealed statistically significant improvement in all disease activity parameters measured. The percentage improvements were similar in groups treated with MTX and LEF and--except for VAS--significantly greater in the group treated with a biologic agent. Disease activity assessed by DAS 28 decreased significantly in all groups: the results were comparable in groups treated with MTX and LEF and significantly more prominent in the group treated with a TNF-alpha blocker. The ACR 20, 50 and 70 improvements amounted, respectively: 100, 50 and 7% in MTX group 87, 60 and 13% in LEF group and 100, 83 and 50% in a biologic agent group. The study revealed equal effectiveness of MTX and LEF in reducing disease activity in rheumatoid arthritis. The efficacy of a TNF-alpha blocker combined with MTX was higher than that of each conventional DMARDs, especially with regard to ACR 70 criteria (considerable improvement after treatment). LEF was equally effective as MTX in patients unable to continue MTX treatment due to the drug's ineffectiveness.", "To evaluate the ability of tocilizumab (a humanised anti-IL-6 receptor antibody) monotherapy to inhibit progression of structural joint damage in patients with RA.\n In a multi-centre, x ray reader-blinded, randomised, controlled trial, 306 patients with active RA of <5 years' duration were allocated to receive either tocilizumab monotherapy at 8 mg/kg intravenously every 4 weeks or conventional disease-modifying antirheumatic drugs (DMARDs) for 52 weeks. Radiographs of hands and forefeet were scored by the van der Heijde modified Sharp method.\n Patients had a mean disease duration of 2.3 years and a disease activity score in 28 joints of 6.5 at baseline. Mean total modified Sharp score (TSS) was 29.4, which was very high despite the relatively short disease duration. At week 52, the tocilizumab group showed statistically significantly less radiographic change in TSS (mean 2.3; 95% CI 1.5 to 3.2) than the DMARD group (mean 6.1; 95% CI 4.2 to 8.0; p<0.01). Tocilizumab monotherapy also improved signs and symptoms. The overall incidences of AEs were 89% and 82% (serious AEs: 18% and 13%; serious infections: 7.6% and 4.1%) in the tocilizumab and DMARD groups, respectively.\n Tocilizumab monotherapy was generally well tolerated and provided radiographic benefit in patients with RA.", "One hundred thirty-one patients with rheumatoid arthritis treated with either azathioprine sodium (n = 37, 102.7 +/- 32.9 mg/d) or methotrexate sodium (n = 94, 8.4 +/- 3.0 mg/wk) were followed up for 38 +/- 23.3 months to determine the nature, frequency, and potential predictors of \"major\" toxic reactions. Thirty-one methotrexate-treated patients (33%) and 11 patients (30%) receiving azathioprine experienced a major toxic reaction during the study period. With the case-control method, no predictors of major toxic reactions secondary to azathioprine therapy were found. Sex, drug dosage, response to prior slow-acting antirheumatic drug therapy, concurrent use of salicylates, and age did not predict major toxic reactions secondary to methotrexate treatment, but the methotrexate-treated patients who experienced a major toxic reaction had a significantly greater mean level of blood urea nitrogen at the time of their reaction compared with the control group. Life-table analysis suggested toxic reactions posed a greater risk of treatment termination in methotrexate-treated patients compared with the lack or loss of efficacy. This trend was not apparent in the azathioprine group. The majority of patients in each treatment group (79 for methotrexate and 29 for azathioprine) experienced one or more \"minor\" toxic reactions during the follow-up period.", "There are insufficient data on the effects of long-term intensive exercise in patients with rheumatoid arthritis (RA). We undertook this randomized, controlled, multicenter trial to compare the effectiveness and safety of a 2-year intensive exercise program (Rheumatoid Arthritis Patients In Training [RAPIT]) with those of physical therapy (termed usual care [UC]).\n Three hundred nine RA patients were assigned to either the RAPIT program or UC. The primary end points were functional ability (assessed by the McMaster Toronto Arthritis [MACTAR] Patient Preference Disability Questionnaire and the Health Assessment Questionnaire [HAQ]) and the effects on radiographic progression in large joints. Secondary end points concerned emotional status and disease activity.\n After 2 years, participants in the RAPIT program showed greater improvement in functional ability than participants in UC. The mean difference in change of the MACTAR Questionnaire score was 2.6 (95% confidence interval [95% CI] 0.1, 5.2) over the first year and 3.1 (95% CI 0.7, 5.5) over the second year. After 2 years, the mean difference in change of the HAQ score was -0.09 (95% CI -0.18, -0.01). The median radiographic damage of the large joints did not increase in either group. In both groups, participants with considerable baseline damage showed slightly more progression in damage, and this was more obvious in the RAPIT group. The RAPIT program proved to be effective in improving emotional status. No detrimental effects on disease activity were found.\n A long-term high-intensity exercise program is more effective than UC in improving functional ability of RA patients. Intensive exercise does not increase radiographic damage of the large joints, except possibly in patients with considerable baseline damage of the large joints." ]

[ "21387176", "21888842", "17931895", "18056488", "21435907", "21670709", "3056948", "18823799", "9480606" ]

[ "The clinical benefit of medial support screws in locking plating of proximal humerus fractures: a prospective randomized study.", "[Surgical treatment for proximal humerus fracture].", "Primary hemiarthroplasty in four-part fractures of the proximal humerus: randomized trial of two different implant systems.", "Immediate mobilization compared with conventional immobilization for the impacted nonoperatively treated proximal humeral fracture. A randomized controlled trial.", "Internal fixation versus nonoperative treatment of displaced 3-part proximal humeral fractures in elderly patients: a randomized controlled trial.", "Are polyaxially locked screws advantageous in the plate osteosynthesis of proximal humeral fractures in the elderly? A prospective randomized clinical observational study.", "Transcutaneous reduction and external fixation of displaced fractures of the proximal humerus. A controlled clinical trial.", "A multicenter, prospective, randomized, controlled trial of open reduction--internal fixation versus total elbow arthroplasty for displaced intra-articular distal humeral fractures in elderly patients.", "[Prosthetic humeral head replacement in dislocated humerus multi-fragment fracture in the elderly--an alternative to minimal osteosynthesis?]." ]

[ "The purpose of this study was to evaluate the clinical benefit of medial support screws for locking plating of proximal humerus fractures.\n Seventy-two consecutive patients underwent prospective treatment for proximal humerus fractures with locking plates between October 2007 and September 2008. Sixty-eight patients accomplished a mean 30.8-month follow-up and were randomized into two groups: 39 patients were treated with only a locking plate and were classified in the -MSS (medial support screw) group, and 29 patients were included in the + MSS group, which were fixed with additional medial support screws. Clinical and radiological investigations were performed in both groups.\n The fractures united at an average of 13.6 weeks after final surgery. Comparably better shoulder function recovery was achieved in the +MSS group with regard to the Constant shoulder score (P = 0.01), with the respective excellent and good rates of 79% and 62%. Eleven patients developed various complications. A statistical difference (P = 0.036) was observed regarding the failure rate (23.1% in the -MSS group vs. 3.4% in the +MSS group). The early loss of fixation was related to higher age (P < 0.001) and less initial neck-shaft angle (NSA) (P = 0.011) of the patients. However, bone mineral density was not significantly associated with loss of fixation (P = 0.076). Although no difference was found in all types of the fractures between the +MSS and -MSS groups regarding immediate postoperative NSA, we observed a significantly lower final NSA in the -MSS group and greater secondary angle loss in the subgroup of Neer three-part (P = 0.033 and 0.015, respectively) and four-part fractures (P = 0.043 and 0.027).\n Anatomical reduction can substantially decrease the risk of postoperative failure in locking plating of proximal humerus fractures. Medial support for proximal humerus fractures seems to have no benefits in Neer two-part fractures. However, the additional medial support screws inserted into the medio-inferior region of the humeral head may help to enhance mechanical stability in complex fractures and allow for better maintenance of reduction.", "The aim of the study was to compare the medical aspects of alternative surgical methods for treatment of proximal humerus fractures in specific indications (two- and three- fragment fractures).\n A prospective randomised study on surgical treatment of two- and three-fragment fractures of the proximal humerus was carried out at the Department of Surgery, University Hospital in Hradec Králové, from January 2006 till January 2010. The study comprised patients with proximal humerus fractures indicated for surgical treatment. Study inclusion criteria were as follows: informed consent, AO fracture types A2, A3, B1 or C1, age between 18 and 80 years, and patient compliance. Exclusion criteria included open fracture, associated injury (AIS . 2), open growth plates, or such state of the patient's health that would limit the extent of surgery. Two groups were compared. One included patients treated by the Zifko method of minimally invasive osteosynthesis with intramedullary K-wire insertion (MIO group) and the other (ORIF group) consisted of patients undergoing open reduction with angle-stable osteosynthesis using a Philos plate (Synthes, Switzerland). The patients were randomised to the groups by a computer programme which facilitates the maintenance of homogeneity of the groups compared. The procedure in each patient was based on the sealed-envelope method.\n The ORIF group comprised 28 patients. It took them an average of 27.2 weeks (9-72) to regain normal upper limb function. The final CM score was 86.6% (64-100%) as compared with the healthy limb. Excellent and good results were achieved in 89% of the patients; complications were recorded in 39% of them. The MIO group included 27 patients. The fractures healed in all of them. Normal upper limb function was regained at an average of 21.4 weeks (13-36). The final CM score was 87.5% (52-100%) in comparison with the healthy limb. Excellent and good results were achieved in 89% and complications developed in 33% of the patients.\n The statistical evaluation of the results, using the unpaired t-test, did not show any significant differences either in functional outcomes or the number of complications between the two groups. The only significant difference was found in operative times (117 min and 72 min in ORIF and MIO groups, respectively). The difference in time needed to regain limb function (27 and 21 weeks) was at a marginal level of statistical significance. With both methods 89% of excellent and good results were achieved, and a similar number of patients had complications (11 and 9).", "The objective of this study was to determine the effect of different prosthetic systems on the functional and radiographic outcomes after shoulder arthroplasty for fractures. This study comprised 35 patients (28 women and 7 men) with a mean age of 74 years (range, 56-88 years) who sustained 4-part fractures of the proximal humerus and were randomly allocated to 2 different groups regarding the type of prosthesis. The 2 systems used differ mainly in the type of fixation of the tuberosities. In group 1 (EPOCA), the fixation was achieved with wire cables through a medial and a lateral hole in the stem, whereas in group 2 (HAS), the fixation was performed by use of transosseous braided sutures. After a follow-up of 1 year, the functional and radiographic outcomes were evaluated. The retrieved data demonstrate that rigid fixation and anatomic positioning of the tuberosities (group 1) increase the rate of bony healing superior to all other factors. There was a statistically significant difference regarding the relative individual Constant score (P = .001) and the mean active range of motion (flexion, P < .001; abduction, P = .001; external rotation in adduction, P = .01; and external rotation in 90 degrees abduction, P = .001) when both groups were compared, showing a better outcome in the EPOCA group for all parameters. Radiologic findings, like heterotopic ossification, glenoid erosion, or subluxation, had no significant influence on the outcome in this study. Accurate placement of the tuberosities and healing at the bone-bone interface of the rotator cuff seem to be the most important factors influencing the outcome in prosthetic care of fractures.", "There have been few randomized controlled trials evaluating nonoperative treatment of proximal humeral fractures. To investigate shortening the period of dependence, we assessed the feasibility and efficacy of early mobilization of the shoulder (within three days after the fracture) in comparison with those of conventional three-week immobilization followed by physiotherapy.\n We randomly assigned seventy-four patients with an impacted proximal humeral fracture to receive early passive mobilization or conventional treatment. The primary outcome was the overall shoulder functional status (as measured with the Constant score) at three months. The secondary outcomes were the Constant score at six weeks and at six months, the change in pain (on a visual analog scale), and the active and passive range of motion.\n At three months and at six weeks, the early mobilization group had a significantly better Constant score than did the conventional-treatment group (between-group difference, 9.9 [95% confidence interval, 1.9 to 17.8] [p = 0.02] and 10.1 [95% confidence interval, 2.0 to 18.1] [p = 0.02], respectively) and better active mobility in forward elevation (between-group difference, 12.0 [95% confidence interval, 1.7 to 22.4] [p = 0.02] and 28.1 [95% confidence interval, 7.1 to 49.1] [p = 0.01], respectively). At three months, the early mobilization group had significantly reduced pain compared with the conventional-treatment group (between-group difference, 15.7 [95% confidence interval, 0.52 to 30.8] [p = 0.04]). No complications in displacement or nonhealing were noted.\n Early mobilization for impacted nonoperatively treated proximal humeral fractures is safe and is more effective for quickly restoring the physical capability and performance of the injured arm than is conventional immobilization followed by physiotherapy.", "The aim of the study was to report the 2-year outcome after a displaced 3-part fracture of the proximal humerus in elderly patients randomized to treatment with a locking plate or nonoperative treatment.\n We included 60 patients, mean age 74 years (range, 56-92), 81% being women. The main outcome measures were the Constant and Disabilities of the Arm, Shoulder and Hand (DASH) scores and the health-related quality of life (HRQoL) according to the EQ-5D.\n At the final 2-year follow-up, the results for range of motion (ROM), function and HRQoL were all in favor of the locking plate group. The mean flexion in the locking plate group was 120° compared to 111° in the nonoperative group (P = .36) and the mean abduction was 114° compared to 106° (P = .28). The corresponding values for the Constant score were 61 versus 58 (P = .64), for DASH 26 versus 35 (P = .19), and the mean EQ-5D (index) score was 0.70 compared to 0.59 (P = .26). In spite of good primary reduction in 86% of the fractures in the locking plate group, 13% of the patients had a fracture complication requiring a major reoperation and 17% had a minor reoperation.\n The results of our study indicate an advantage in functional outcome and HRQoL in favor of the locking plate compared to nonoperative treatment in elderly patients with a displaced 3-part fracture of the proximal humerus, but at the cost of additional surgery in 30% of the patients.\n Copyright © 2011 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.", "To evaluate the results of plate osteosynthesis using either polyaxial or nonpolyaxially locked screw-plate systems in proximal humeral fractures in the elderly.\n Prospective, randomized.\n Level I trauma center.\n Fifty-six patients (older than 60 years) with isolated, displaced three- and four-part fractures were included. Twenty-five patients (median age, 75.5 years) were randomized to a polyaxial locking screw plate (Group 1), whereas 31 patients (median age, 72 years) were treated with a locking screw plate (Group 2). Follow-up evaluations were performed 3, 6, and 12 months postoperatively using the Simple Shoulder Test, Disabilities of the Arm, Shoulder and Hand score, and Constant score as well as radiographs. The results and the complications were compared between both groups.\n Forty-eight patients were available for follow-up (Group 1, 20 of 25; Group 2, 28 of 31). The Simple Shoulder Test, Disabilities of the Arm, Shoulder and Hand, and Constant score improved significantly from 3 to 12 months and did not differ between groups. Twelve months after the index procedure, the Simple Shoulder Test score was 8.6 ± 3.2 points in Group 1 and 9.7 ± 1.8 points in Group 2. The Disabilities of the Arm, Shoulder and Hand score was 17.8 ± 16.2 in Group 1 and 15.7 ± 11.8 in Group 2. The mean Constant score amounted to 73% ± 17% in Group 1 and 81% ± 13% in Group 2. There were six complications in Group 1 and eight in Group 2.\n Both the functional outcomes and the rate of complications after polyaxial locked plate osteosynthesis of proximal humeral fractures in elderly patients were comparable to those treated with nonpolyaxial implants. Despite the theoretical advantages of polyaxial locked plating in proximal humerus fractures, this study could not show a verifiable clinical advantage of these plates.", "A consecutive series of 31 displaced fractures of the proximal humerus were randomly selected for treatment either by closed manipulation or by transcutaneous reduction and external fixation. Follow-up assessed the quality of reduction and healing as well as the functional outcome. The external fixation method gave better reduction, safer healing and superior function.", "We conducted a prospective, randomized, controlled trial to compare functional outcomes, complications, and reoperation rates in elderly patients with displaced intra-articular, distal humeral fractures treated with open reduction-internal fixation (ORIF) or primary semiconstrained total elbow arthroplasty (TEA). Forty-two patients were randomized by sealed envelope. Inclusion criteria were age greater than 65 years; displaced, comminuted, intra-articular fractures of the distal humerus (Orthopaedic Trauma Association type 13C); and closed or Gustilo grade I open fractures treated within 12 hours of injury. Both ORIF and TEA were performed following a standardized protocol. The Mayo Elbow Performance Score (MEPS) and Disabilities of the Arm, Shoulder and Hand (DASH) score were determined at 6 weeks, 3 months, 6 months, 12 months, and 2 years. Complication type, duration, management, and treatment requiring reoperation were recorded. An intention-to-treat analysis and an on-treatment analysis were conducted to address patients randomized to ORIF but converted to TEA intraoperatively. Twenty-one patients were randomized to each treatment group. Two died before follow-up and were excluded from the study. Five patients randomized to ORIF were converted to TEA intraoperatively because of extensive comminution and inability to obtain fixation stable enough to allow early range of motion. This resulted in 15 patients (3 men and 12 women) with a mean age of 77 years in the ORIF group and 25 patients (2 men and 23 women) with a mean age of 78 years in the TEA group. Baseline demographics for mechanism, classification, comorbidities, fracture type, activity level, and ipsilateral injuries were similar between the 2 groups. Operative time averaged 32 minutes less in the TEA group (P = .001). Patients who underwent TEA had significantly better MEPSs at 3 months (83 vs 65, P = .01), 6 months (86 vs 68, P = .003), 12 months (88 vs 72, P = .007), and 2 years (86 vs 73, P = .015) compared with the ORIF group. Patients who underwent TEA had significantly better DASH scores at 6 weeks (43 vs 77, P = .02) and 6 months (31 vs 50, P = .01) but not at 12 months (32 vs 47, P = .1) or 2 years (34 vs 38, P = .6). The mean flexion-extension arc was 107 degrees (range, 42 degrees -145 degrees) in the TEA group and 95 degrees (range, 30 degrees -140 degrees) in the ORIF group (P = .19). Reoperation rates for TEA (3/25 [12%]) and ORIF (4/15 [27%]) were not statistically different (P = .2). TEA for the treatment of comminuted intra-articular distal humeral fractures resulted in more predictable and improved 2-year functional outcomes compared with ORIF, based on the MEPS. DASH scores were better in the TEA group in the short term but were not statistically different at 2 years' follow-up. TEA may result in decreased reoperation rates, considering that 25% of fractures randomized to ORIF were not amenable to internal fixation. TEA is a preferred alternative for ORIF in elderly patients with complex distal humeral fractures that are not amenable to stable fixation. Elderly patients have an increased baseline DASH score and appear to accommodate to objective limitations in function with time.", "In a prospective randomised study, comprising 30 aged patients with fractures of the proximal humerus (4-fragment fractures according to Neer) minimal osteosynthesis was compared to primary endoprosthetic replacement. The Constant score was used for evaluation during follow-up. After one year the results were similar in both groups. There were two complications necessitating revision surgery among the patients with minimal osteosynthesis and in four cases the implants had to be removed. In the group with primary endoprosthetic repair neither complications nor revision surgery occurred. Primary endoprosthetic replacement for the treatment of proximal humeral fractures appears as a therapeutic option with a low complication rate and a satisfying functional outcome. In older patients we need a safe mode of therapy permitting early mobilization and quick discharge from the hospital back to the patient's home. Endoprosthetic replacement fulfils these demands since it resembles a \"one time surgery\" without the risk of revision surgery for implant loosening, pseudarthrosis or ischemic necrosis of the humeral head." ]

[ "8372870", "10586979", "15951574", "48000", "2698591", "11194427", "1442986", "14557006", "1584259" ]

[ "Insulin-requiring diabetes in pregnancy: a randomized trial of active induction of labor and expectant management.", "Treatment of women with an abnormal glucose challenge test (but a normal oral glucose tolerance test) decreases the prevalence of macrosomia.", "Effect of treatment of gestational diabetes mellitus on pregnancy outcomes.", "Elective induction of labour. A randomised prospective trial.", "Comparison of induced versus non-induced labor in post-term pregnancy. A randomized prospective study.", "A randomised controlled trial of dietary energy restriction in the management of obese women with gestational diabetes.", "Randomized trial of human versus animal species insulin in diabetic pregnant women: improved glycemic control, not fewer antibodies to insulin, influences birth weight.", "Maternal metabolic control and perinatal outcome in women with gestational diabetes treated with regular or lispro insulin: comparison with non-diabetic pregnant women.", "Induction of labor as compared with serial antenatal monitoring in post-term pregnancy. A randomized controlled trial. The Canadian Multicenter Post-term Pregnancy Trial Group." ]

[ "Our purpose was to assess whether a program of expectant management of uncomplicated pregnancies in mothers with insulin-requiring gestational or pregestational class B reduces the incidence of cesarean birth.\n Two hundred women with uncomplicated, insulin-requiring diabetes at 38 weeks' gestation who were compliant with care and whose infants were judged appropriate for gestational age were randomly assigned to (1) active induction of labor within 5 days or (2) expectant management. The expectant management group was monitored with weekly physical examination and twice-weekly nonstress tests and amniotic fluid volume estimation until delivery.\n Expectant management increased the gestational age at delivery by 1 week. Approximately half (49%) of the mothers in the expectant management group required induction of labor for obstetric indications. The cesarean delivery rate was not significantly different in the expectant management group (31%) from the active induction group (25%). The mean birth weight (3672 +/- 407 gm) and percentage large for gestational age, as defined by birth weight > or = 90th percentile, of infants in the expectantly managed group (23%) was greater than those in the active induction group (3466 +/- 372 gm, p < 0.0001, 10% large for gestational age). This difference persisted after controlling for gestational age and maternal age and body weight (p < 0.01).\n In women with uncomplicated insulin-requiring gestational or class B pregestational diabetes, expectant management of pregnancy after 38 weeks' gestation did not reduce the incidence of cesarean delivery. Moreover, there was an increased prevalence of large-for-gestational-age infants (23% vs 10%) and shoulder dystocia (3% vs 0%). Because of these risks, delivery should be contemplated at 38 weeks and, if not pursued, careful monitoring of fetal growth must be performed.", "Infant macrosomia is a serious medical concern. Pregnant women who do not meet the specific diagnosis for gestational diabetes may still have glucose-mediated macrosomia. In Santa Barbara County all pregnant women are screened for gestational diabetes at 24-28 weeks with a 50-g, 1-hr glucose challenge test (GCT). All patients who fail this test are placed on a standard euglycemic diet (40% carbohydrate, 20% protein, 40% fat) and perform home glucose monitoring of fasting and postprandial glucose levels. The objective of this study was to examine the effectiveness of this treatment program in decreasing infant macrosomia, maternal and infant morbidity, maternal complications, and operative delivery. We studied 103 women who had a positive GCT, but a negative 100-g, 3-hr oral glucose tolerance test (OGTT). The women were randomly assigned to either experimental or control groups with experimental women receiving dietary counseling and home glucose monitoring instruction (HBGM). HBGM diaries were reviewed weekly by clinic nurses. All women had hemoglobin A1c (HbA1c) tests at 28 and 32 weeks. Maternal and fetal charts were reviewed to determine delivery type and complications, indications for cesarean section (C-section), and infant gestational age, gender, Apgar scores, birth weight, morbidities, and congenital anomalies. Of the 103 women, 5 women required insulin treatment, 1 woman had an abortion, and 14 women were indeterminate regarding compliance or were control women who received diet counseling and HBGM. The results are based on 83 women--48 control and 35 experimental. There were no significant differences between the groups for age, parity, or weight at 28-30 weeks or 37 weeks to delivery, or HbA1c at 28 weeks. HbA1c was significantly higher in control women at 32 weeks. Birth weight expressed in grams or as a percentile specific for gender, ethnicity, and gestational age was significantly higher in control infants. Birth weight was significantly correlated with maternal intake weight, weight at 28-30 weeks, and weight at delivery and with HbA1c at 32 weeks' gestation. There were no significant differences between groups for maternal complications. Groups were significantly different for mode of delivery with experimental women having more induced vaginal deliveries but fewer repeat C-sections than control women. Groups were not different for primary C-sections. Women who fail the GCT, but not the OGTT and thus do not receive the diagnosis of GDM are still at risk for delivering a macrosomic infant and operative delivery. Our program of treatment for all women who fail the GCT improves outcome by reducing infant birth weight and the number of cesarean sections.", "We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications.\n We randomly assigned women between 24 and 34 weeks' gestation who had gestational diabetes to receive dietary advice, blood glucose monitoring, and insulin therapy as needed (the intervention group) or routine care. Primary outcomes included serious perinatal complications (defined as death, shoulder dystocia, bone fracture, and nerve palsy), admission to the neonatal nursery, jaundice requiring phototherapy, induction of labor, cesarean birth, and maternal anxiety, depression, and health status.\n The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group (1 percent vs. 4 percent; relative risk adjusted for maternal age, race or ethnic group, and parity, 0.33; 95 percent confidence interval, 0.14 to 0.75; P=0.01). However, more infants of women in the intervention group were admitted to the neonatal nursery (71 percent vs. 61 percent; adjusted relative risk, 1.13; 95 percent confidence interval, 1.03 to 1.23; P=0.01). Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group (39 percent vs. 29 percent; adjusted relative risk, 1.36; 95 percent confidence interval, 1.15 to 1.62; P<0.001), although the rates of cesarean delivery were similar (31 percent and 32 percent, respectively; adjusted relative risk, 0.97; 95 percent confidence interval, 0.81 to 1.16; P=0.73). At three months post partum, data on the women's mood and quality of life, available for 573 women, revealed lower rates of depression and higher scores, consistent with improved health status, in the intervention group.\n Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman's health-related quality of life.", "In a prospective, randomised trial, 111 obstetrically normal pregnant women, who had elective induction of labour performed between 39 and 40 weeks, were compared with 117 controls who were managed expectantly until 41 weeks. Compared with the controls, the patients who had elective induction of labour had significantly less meconium staining in labour and a smaller blood-loss after delivery. The mean length of labour, the amount of pethidine used, and the Apgar scores at 1 minute were similar in the two groups. In the electively induced group, the caesarean-section rate was lower and the use of epidural analgesia more common than in the controls, but the differences were mot statistically signficant. The hour of delivery was similar in the two groups, suggesting that convenience to medical and nursing staff would not be greatly changed by elective induction of labour. There was no evidence that the hazards to mother and child were increased by elective induction, and its use might improve perinatal mortality by reducing the number of unexplained mature stillbirths.", "To determine the proper management of pregnancy in uncomplicated cases going beyond 42 weeks.\n Randomized controlled trial of induction of labor at or shortly after the 42-week limit, versus close monitoring without induction except when indicated for medical reasons.\n Hospital's obstetrical department\n 188 pregnant women, randomly allocated to two groups with 94 in each.\n Induction of labor by stripping of membranes and i.v. oxytocin infusion, with artificial rupture of membranes when the cervical opening was 3 cm or more in diameter. The control group was followed with clinical, biochemical and electronic tests, intervention being applied according to needs.\n Frequency and modes of operative delivery, maternal and perinatal morbidity and mortality.\n The distribution of gestational age (in weeks) at birth was almost identical in the two groups, but there were more operative deliveries in the control group than in the induction group (64 versus 48, p less than 0.05). Maternal complications and perinatal morbidity rates were equally distributed between the groups. There was one perinatal death in the induction group and two deaths among the controls.\n With due reservation for small numbers, routine induction after term may result in fewer operative deliveries. No other advantage has been demonstrated when compared with close monitoring and intervention when medically indicated.", "A randomised controlled trial was designed to determine the effect of moderate 30% maternal dietary energy restriction on the requirement for maternal insulin therapy and the incidence of macrosomia in gestational diabetes. Although the control group restricted their intake to a level similar to that of the intervention group (6,845 kiloJoules (kJ) versus 6,579 kJ), the resulting cohort could not identify any adverse effect of energy restriction in pregnancy. Energy restriction did not alter the frequency of insulin therapy (17.5% in the intervention group and 16.9% in the control group). Mean birthweight (3,461 g in the intervention group and 3,267 g in the control group) was not affected. There was a trend in the intervention group towards later gestational age at commencement of insulin therapy (33 weeks versus 31 weeks) and lower maximum daily insulin dose (23 units versus 60 units) which did not reach statistical significance. Energy restriction did not cause an increase in ketonemia.", "Macrosomia occurs in infants of diabetic mothers in spite of \"nearly normal maternal blood glucose levels\" with insulin treatment. Insulin antibodies may carry bound insulin into the fetal blood and thus may be associated with fetal hyperinsulinemia and macrosomia in these infants. Our objective was to test the hypothesis that human insulin is associated with lower insulin antibody levels and less macrosomia than is animal species insulin.\n Forty-three insulin-requiring pregnant (< 20 weeks' gestation) women, previously treated with animal insulin, were randomized to human and animal insulins and studied at weeks 10 through 20, 24, 28, 32, 36, and 38, at delivery, and at 3 months post partum. Infant blood was drawn at delivery (cord) and at 1 day and 3 months post partum 1 hour after a glucose-amino acid challenge.\n Women receiving human insulin required significantly less insulin per kilogram of body weight and showed significant dampening of glucose excursions (p < 0.05 for each comparison). Infants born to mothers receiving human insulin weighed 2880 +/- 877 gm compared with 3340 +/- 598 gm for infants of women treated with animal insulin (p < 0.05). There was no difference in insulin antibody levels between groups for either mothers or infants. Infants born to mothers receiving human insulin had a 1 hour C-peptide level after the glucose-amino acid challenge at 3 months of age of 0.21 +/- 0.13 pmol/ml compared with 0.32 +/- 0.13 pmol/ml (p = 0.01).\n Administration of human insulin to pregnant diabetic women has a therapeutic advantage over animal insulin, with less maternal hyperglycemia or hypoglycemia, fewer larger-for-gestational-age infants, and less neonatal hyperinsulinemia. Our data do not support the hypothesis that maternal antibodies to insulin influence infant birth weight.", "To compare maternal glucose levels and neonatal outcome, achieved in women with gestational diabetes (GDM) receiving either regular insulin or insulin lispro, with those of a control group of non-diabetic pregnant women.\n We enrolled 49 pregnant women with GDM, randomly allocated to the treatment with either insulin lispro (n=25) or regular insulin (n=24), and 50 pregnant women with normal GCT, matched for age, parity, pre-pregnancy weight and BMI, who formed the control group. All the women were caucasian, non-obese, with a singleton pregnancy and delivered term live born infants. Women of both groups were requested to perform a blood glucose profile (consisting of nine determinations: fasting/pre-prandial, 1 and 2h post-prandial) every week from the time of diagnosis to 38 weeks (study subgroups) or every 2 weeks from 28 to 38 weeks' gestation (control group).\n Overall pre-prandial blood glucose values in diabetic women were significantly higher than those of controls; at the 1h post-prandial time point, blood glucose values of GDM women receiving insulin lispro were similar to those of controls, whereas in the regular group they were significantly higher. Overall, both the lispro and regular insulin obtained optimal metabolic control at the 2h post-prandial time point, although near-normal blood glucose levels 2h after lunch could be observed only in the lispro group. There were no statistically significant differences between the groups in neonatal outcome and anthropometric characteristics; however, the rate of infants with a cranial-thoracic circumference (CC/CT) ratio between the 10th and the 25th percentile was significantly higher in the group treated with regular insulin in comparison to the lispro and control groups.\n Fasting/pre-prandial and 1h post-prandial maternal blood glucose levels in non-diabetic pregnant women fell well below the currently accepted criteria of glycemic normality in diabetic pregnancies. In women with GDM, the use of insulin lispro enabled the attainment of near-normal glucose levels at the 1h post-prandial time point and was associated with normal anthropometric characteristics; the use of regular insulin was not able to blunt the 1h peak post-prandial response to a near-normal extent and resulted in infants with a tendency toward the disproportionate growth. Insulin lispro can be regarded as a valuable option for the treatment of gestational diabetes.", "The rates of perinatal mortality and neonatal morbidity are higher for post-term pregnancies than for term pregnancies. It is not known, however, whether the induction of labor results in better outcomes than does serial fetal monitoring while awaiting spontaneous labor.\n We studied 3407 women with uncomplicated pregnancies of 41 or more weeks' duration. The women were randomly assigned to undergo induction of labor or to have serial antenatal monitoring and spontaneous labor unless there was evidence of fetal or maternal compromise, in which case labor was induced or cesarean section was performed. In the induction group, labor was induced by the intracervical application of prostaglandin E2. Serial antenatal monitoring consisted of counts of fetal kicks, nonstress tests, and assessments of amniotic-fluid volume. The outcomes we measured were the rates of perinatal mortality, neonatal morbidity, and delivery by cesarean section.\n Among the 1701 women in the induction group, 360 (21.2 percent) underwent cesarean section, as compared with 418 (24.5 percent) of the 1706 women in the monitoring group (P = 0.03). This difference resulted from a lower rate of cesarean section performed because of fetal distress among the women in the induction group (5.7 percent vs. 8.3 percent, P = 0.003). When two infants with lethal congenital anomalies were excluded, there were no perinatal deaths in the induction group and two stillbirths in the monitoring group (P not significant). The frequency of neonatal morbidity was similar in the two groups.\n In post-term pregnancy, the induction of labor results in a lower rate of cesarean section than serial antenatal monitoring; the rates of perinatal mortality and neonatal morbidity are similar with the two approaches to management." ]

[ "6803118", "6811710", "16330203", "6403808", "17324657", "8768018", "15684319", "6406649", "6119492" ]

[ "A prospective randomized clinical trial of total parenteral nutrition in children with cancer.", "Comparison of morbidity in children requiring abdominal radiation and chemotherapy, with and without total parenteral nutrition.", "Parenteral nutrition is not superior to replacement fluid therapy for the supportive treatment of chemotherapy induced oral mucositis in children.", "Effect of total parenteral nutrition on marrow recovery during induction therapy for acute nonlymphocytic leukemia in childhood.", "Nutrition support using the American Dietetic Association medical nutrition therapy protocol for radiation oncology patients improves dietary intake compared with standard practice.", "[Total enteral nutrition versus mixed enteral and parenteral nutrition in patients at an intensive care unit].", "Dietary counseling improves patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy.", "The favorable effect of early parenteral feeding on survival in head-injured patients.", "Preoperative parenteral feeding in patients with gastrointestinal carcinoma." ]

[ "A prospective randomized clinical trial was undertaken to test the efficacy of total parenteral nutrition (TPN) among previously untreated children receiving abdominal/pelvic irradiation with or without adjuvant chemotherapy who were at risk for weight loss, malnutrition, and complications from treatment. Children were evaluated by weight/height determinations, anthropomorphic measurements, and laboratory studies. TPN was associated with an improved nutritional status during therapy as compared with control patients on ad libitum intake. However, when TPN was discontinued, weight declined and there were no differences among treated and control patients detected at three-month follow-up. Likewise there was no obvious effect from TPN on tolerance to therapy in the adequately nourished child. TPN as initial supportive therapy should be reserved for those children who are malnourished or marginally malnourished at the time of presentation. Close nutritional assessment during treatment is essential since approximately 25% of children undergoing abdominal/pelvic radiotherapy with chemotherapy can be expected to become malnourished during an initial course of therapy.", "We evaluated the effectiveness of total parenteral nutrition and placing the \"bowel at rest,\" as compared to that of ad libitum food intake, on nutritional status and tolerance to combined chemotherapy and radiotherapy in a randomized, prospective trial in children with previously untreated malignancy requiring abdominal and pelvic irradiation and chemotherapy. Administration of TPN was found to be safe and efficacious in maintaining the children in good nutritional status during combined therapy; one-third of the control patients became malnourished and required TPN. There was no beneficial effect of \"bowel at rest\" and TPN on the ability of patients to tolerate combined therapies in terms of decreased toxicity; however, use of TPN was associated with improved adherence to chemotherapy schedules. Following termination of TPN or ad libitum food intake, and while receiving chemotherapy, the majority of the children who had previously received TPN lost significant weight. To date there has been no difference in mortality rate between the control and TPN groups. Although we conclude that TPN per se had little beneficial effect beyond that of maintaining good nutritional status, every child undergoing intensive combined therapy should have early and periodic assessments of nutritional status, so that the early signs of malnutrition can be detected, and the adverse effects of malnutrition can be prevented by nutritional replenishment, by TPN, or by other methods.", "Many paediatric oncology centres apply parenteral nutrition (PN) in children with severe oral mucositis after chemotherapy. However, no convincing data exist to support this treatment strategy. The aim of our study was to elucidate a possible advantage of PN versus intravenous replacement fluid therapy (FT). In a prospective randomized study, 30 children with mucositis WHO grade IV were assigned to receive either PN or intravenous replacement FT. Weight, total body water, fat-free mass (measured by impedance analysis) and peripheral white blood cells were assessed daily. For aspects of quality of life and economics, the length of hospital stay, the incidence of infections, the days on intravenous antibiotics and delay of scheduled chemotherapy were examined. Children with PN gained body weight significantly compared to baseline and to FT due to an augmentation of fat mass while total body water and fat-free mass significantly decreased. In children with FT, body weight remained stable while total body water and fat-free mass significantly increased, thereby loosing fat mass. We observed no differences in recovery of peripheral white blood cells (WBC), incidence of infections, hospitalization time, days on intravenous antibiotics, days on opioid analgesics and delay of the next scheduled chemotherapy cycle. Although children with PN gained weight in form of fat mass, this did not translate into a clinical benefit for the patients such as earlier recovery of WBC counts, shorter hospitalization time, a decreased use of analgesics or less delay of the next scheduled chemotherapy cycle. Our findings therefore do not support the hypothesis that PN is superior to FT when used for less than 10 days for oral mucositis.", "Ten well-nourished children with acute nonlymphocytic leukemia (ANLL) were randomly assigned to groups that received (a) total parenteral nutrition (TPN) throughout the period of induction therapy or (b) standard nutritional support. Body mass and skin hypersensitivity reactions were better maintained in experimental patients. Patients on TPN had higher total white blood counts, absolute granulocyte counts, and platelet counts than did control patients during the course. No difference was apparent in the frequency of febrile episodes, or other aspects of the patients' courses. This preliminary report suggests that intensive nutritional support may accelerate the recovery of normal marrow function during induction therapy for ANLL.", "A randomized controlled trial previously conducted in radiation oncology patients demonstrated that nutrition intervention had a beneficial impact on body weight, nutritional status, and quality of life compared with standard practice, but it did not report on dietary intake data.\n To determine the impact of nutrition intervention compared with standard practice on dietary intake in outpatients receiving radiotherapy.\n Prospective, randomized, controlled trial.\n Sixty consecutive radiation oncology outpatients (51 men and nine women; age 61.9+/-14 years [mean+/-standard deviation]).\n Australian private radiotherapy facility.\n Patients were randomly assigned to receive either nutrition intervention (n=29) (nutrition counseling following the American Dietetic Association [ADA] medical nutrition therapy [MNT] protocol for radiation oncology) or standard practice (n=31) (general nutrition talk and booklet).\n Dietary intake (protein, energy, fiber) assessed at baseline and at 4, 8, and 12 weeks after starting radiotherapy.\n Repeated-measures analysis of variance done on an intention to treat basis.\n The nutrition intervention group had a higher mean total energy (P=0.029) and protein intake (P<0.001) compared with the standard practice group. Mean intake per kilogram of body weight for the nutrition intervention group ranged from 28 to 31 kcal/kg/day compared with 25 to 29 kcal/kg/day for the standard practice group (P=0.022). The nutrition intervention group had a higher mean protein intake (1.1 to 1.3 g/kg/day) compared with the standard practice group (1.0 to 1.1 g/kg/day) (P=0.001). Although the change in fiber intake between the groups was not significant, there was a trend in the anticipated direction (P=0.083).\n Intensive nutrition intervention following the ADA MNT protocol results in improved dietary intake compared with standard practice and seems to beneficially impact nutrition-related outcomes previously observed in oncology outpatients receiving radiotherapy. The ADA MNT protocol for radiation oncology is a useful guide to the level of nutrition support required.", "To compare metabolic, nutritional and epidemiological data in two groups of patients, one receiving total enteral nutrition, via nasoenteric tube, and one receiving both enteral and parenteral nutrition.\n A prospective, randomized study.\n A general ICU, with both medical and surgical patients, in a big regional University and National Health Service hospital.\n 24 patients requiring Intensive Care after major surgery or because suffering from severe head injury or major neurological impairment.\n All patients initially received total parenteral nutrition: after 4 days 12 patients were \"weaned\" to total enteral nutrition and 12 stayed on mixed parenteral and enteral nutrition. LABORATORY INVESTIGATIONS AND OBSERVATIONAL DATA: Blood levels of albumin, prealbumin, transferrin, ALT, AST, bilirubin, blood urea, blood glucose, total linfocite count, and nutritional and epidemiological data such as nitrogen balance, calorie intake, diarrhea incidence, blood and sputum cultures and radiologic evidence of pneumonia are analysed.\n At T1, NET patients were able to reduce their nitrogen losses (0.27.1 g/kg +/-0.12 vs 0.35 +/- 0.13 at TO; p < 0.05) and improve nitrogen balance (-9 +/- 7 vs -2 +/- 6 at T0; p < 0.05); they also had a better total linfocite count (2034 +/- 304 vs. 1413 +/- 360 of the MISTA group; p < 0.05), and a lower incidence of pneumonia as documented by sputum cultures and radiograms.\n Patients fed with both parenteral and enteral nutrition did no better than those on total enteral nutrition as far as nutritional and metabolic indices were concerned; they also seemed more prone to infections than those on total enteral nutrition, indicating that mixed nutrition may result in more stable feeding, but this does not seem to have any beneficial nutritional, immunological and metabolic effect.", "To investigate the impact of dietary counseling or nutritional supplements on outcomes in cancer patients: nutritional, morbidity, and quality of life (QoL) during and 3 months after radiotherapy.\n A total of 111 colorectal cancer outpatients referred for radiotherapy, stratified by staging, were randomly assigned: group 1 (G1; n = 37), dietary counseling (regular foods); group 2 (G2; n = 37), protein supplements; and group 3 (G3; n = 37), ad libitum intake. Nutritional intake (diet history), status (Ottery's Subjective Global Assessment), and QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0) were evaluated at baseline, at the end, and 3 months after radiotherapy.\n At radiotherapy completion, energy intake increased in G1/G2 (P < or = .04), G1 more than G2 (P = .001), and decreased in G3 (P < .01). Protein intake increased in G1/G2 (P < or = .007), G1 less than G2 (not significant), and decreased in G3 (P < .01). At 3 months, G1 maintained nutritional intake and G2/G3 returned to baseline. After radiotherapy and at 3 months, rates of anorexia, nausea, vomiting, and diarrhea were higher in G3 (P < .05). At radiotherapy completion, in G1 all QoL function scores improved proportionally to adequate intake or nutritional status (P < .05); whereas in G2 only three of six function scores improved proportionally to protein intake (P = .04), and in G3 all scores worsened (P < .05). At 3 months, G1 patients maintained/improved function, symptoms, and single-item scores (P < .02); in G2, only few function and symptom scales improved (P < .05); in G3, QoL remained as poor as after radiotherapy. In G1/G2, respectively, improvement/deterioration of QoL correlated with better or poorer intake or nutritional status (P < .003).\n During radiotherapy, both interventions positively influenced outcomes; dietary counseling was of similar or higher benefit, whereas even 3 months after RT, it was the only method to sustain a significant impact on patient outcomes.", "This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p less than 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p less than 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury.", "In a comparative clinical trial to examine the influence of 10 days of preoperative parenteral nutrition (PPN) on the postoperative complication rate for gastrointestinal carcinoma 59 patients (controls) received the regular hospital diet and 66 received PPN. The two groups were similar in nutritional status and in distribution of site and stage of tumour and type of operation. The rates of postoperative wound infection, pneumonia, major complications, and mortality were generally lower in the PPN group, but the differences were significant only for major complications and mortality. The clinical results can be explained by the improvement in various indices of humoral and cellular immunocompetence and the protein status in the PPN group and their deterioration in the control group during the preoperative course." ]

[ "12006305", "10918757", "2258521", "8455920", "12052998", "8248962", "9506598", "12161876", "9133884" ]

[ "Does an integrated care pathway improve processes of care in stroke rehabilitation? A randomized controlled trial.", "The development of a stroke clinical pathway: an experience in a medium-sized community hospital.", "The effect of systematic care planning after acute stroke in general hospital medical wards.", "The critical path method in stroke rehabilitation: lessons from an experiment in cost containment and outcome improvement.", "Integrated care pathways and quality of life on a stroke rehabilitation unit.", "A model for management of patients with stroke during the acute phase. Outcome and economic implications.", "A randomized controlled trial of rehabilitation at home after stroke in southwest Stockholm.", "Variance analysis applied to a stroke pathway: how this can improve efficiency of healthcare delivery.", "Evaluation of a stroke family care worker: results of a randomised controlled trial." ]

[ "to evaluate whether integrated care pathways improve the processes of care in stroke rehabilitation.\n comparison of processes of care data collected in a randomized controlled trial.\n acute stroke patients undergoing rehabilitation randomized to receive integrated care pathways management (n=76) or conventional multidisciplinary care (n=76).\n proportion of patients meeting recommended standards for processes of care using a validated stroke audit tool.\n integrated care pathways methodology was associated with higher frequency of stroke specific assessments, notably testing for inattention (84% versus 60%; P=0.015) and nutritional assessment (74% versus 22%, P<0.001). Documentation of provision of certain information to patients/carers (89% versus 70%; P=0.024) and early discharge notification to general practitioners (80% versus 45%; P<0.001) were also more common in this group. There were no significant differences in the processes of interdisciplinary co-ordination and patient management between the integrated care pathways group and the control group.\n integrated care pathways may improve assessment and communication, even in specialist stroke settings.", "Patients with acute ischemic strokes were studied in a medium-sized community hospital in Mississippi. Studies were done before and after implementation of the stroke clinical care pathway with emphasis on the following clinical indicators: 1) performance of a brain CT scan, 2) the search for the etiology of the stroke, 3) whether the patient was treated emergently for hypertension, 4) the use of measures to prevent deep-vein thrombosis, and 5) prophylactic drug treatment against recurrent stroke after hospital discharge. Following application of the clinical pathway, there was a significant improvement in all the clinical indicators that were felt to require further attention and none had a setback. The length of hospital stay was decreased, and there was no significant increase in the hospital costs in the post-pathway study despite an increase in the number of diagnostic and therapeutic procedures performed. When applied properly, clinical pathways can effectively mobilize hospital resources, maximize quality of care, and at the same time minimize costs.", "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.", "This study tested the effects of a project network technique called the Critical Path Method (CPM) on the costs and outcomes of inpatient team stroke rehabilitation. On admission to a large, academic, inpatient rehabilitation hospital adults who had a recent (< 120 days) stroke were randomly assigned to receive rehabilitation services from a team trained in CPM (N = 53) or from usual care teams (N = 68). Results showed no significant difference between groups in length of stay, hospital charges, or functional status at discharge. CPM may be effective in patient care services that are less influenced by specialization, professional issues, and external regulation and in settings where patient outcomes are relatively fixed and predictable, and medical care is integrated across institutions.", "Integrated care pathways (ICP) may not reduce disability, institutionalization, or duration of hospitalization compared with conventional multidisciplinary team (MDT) care in organized stroke rehabilitation. Their potential to improve patient heath status or satisfaction with care is not known.\n A comparison of quality of life, caregiver strain, and patient/caregiver satisfaction at 6 months after stroke was undertaken in 152 stroke patients randomized to receive ICP or MDT care. Differences in processes of care were recorded with the use of a predefined schedule. Multivariate analyses were undertaken to identify the effect of age, sex, stroke severity, functional status, mood, and use of care pathway on quality of life score.\n The 2 groups were comparable for baseline characteristics of age, sex, stroke severity, and initial disability. MDT care was characterized by greater emphasis on return of higher function and caregiver needs compared with ICP. EuroQol Visual Analogue Scale (EQ-VAS) scores were higher in the MDT group (median, 72 versus 63; P<0.005), who also had higher scores for EuroQol dimension of social functioning (P=0.014). Higher EQ-VAS scores were independently related to MDT care (P=0.04), Rankin score (P=0.01), and psychological function (P<0.0001) but not to age, sex, or stroke severity. There were no significant differences in patient or caregiver satisfaction between the 2 settings.\n Better quality of life in patients receiving conventional MDT care may be attributable to improved social functioning and greater attention to higher function and caregiver needs during rehabilitation.", "The purpose of the study was to develop a clinical pathway for patients with nonhemorrhagic stroke during the acute hospital phase to improve the quality of care and reduce costs.\n The pathway included standard admission orders and a swallow screen on day 1 of hospitalization. Physical therapy, occupational therapy, speech therapy, and social worker assessments were done on day 2. A physiatry consult was performed on day 3 if indicated, and by day 4 a discharge target date and disposition were addressed.\n Outcomes for 121 patients during the first year of pathway implementation are reported. The average length of stay on the acute service decreased from 10.9 days to 7.3 days (P < .05), reducing the charges per patient by 14.6%. Complications in the form of urinary tract infections and aspiration pneumonia rates decreased by 63.2% (P < .05) and 38.7%, respectively.\n We conclude that the implementation of a clinical pathway for patients with acute, nonhemorrhagic stroke resulted in a significant reduction in length of stay, charges, and complications while improving the quality of care.", "This study describes the methodology, patient outcome, and use of hospital and rehabilitation services at 3 months of a population-based randomized controlled trial. The purpose was to evaluate rehabilitation at home after early supported discharge from the Department of Neurology, Huddinge Hospital, for moderately disabled stroke patients in southwest Stockholm.\n The patients were eligible if they were continent, independent in feeding, had mental function within normal limits, and had impaired motor function and/or aphasia 1 week after stroke. Patients were randomized either to early supported discharge with continuity of rehabilitation at home for 3 to 4 months or to routine rehabilitation service in a hospital, day care, and/or outpatient care. The home rehabilitation team consisted of two physical therapists, two occupational therapists, and one speech therapist; one of the therapists was assigned as case manager for the patient. The rehabilitation program at home emphasized a task- and context-oriented approach. The activities were chosen on the basis of the patient's personal interests. Spouses were offered education and individual counseling. A total of 81 patients were followed up for a minimum of 3 months. Patient outcome was assessed by the Frenchay Social Activity Index, Extended Katz Index, Barthel Index, Lindmark Motor Capacity Assessment, Nine-Hole Peg Test, walking speed over 10 m, reported falls, and subjective dysfunction according to the Sickness Impact Profile. Patient use of hospital and home rehabilitation service and patient satisfaction with care were studied.\n Overall there were no statistical significant differences in outcome. Multivariate logistic regression analysis suggested a systematic positive effect for the home rehabilitation group in social activity, activities of daily living, motor capacity, manual dexterity, and walking. A considerable difference in resource use during such a 3-month period was seen. A 52% reduction in hospitalization was observed: from 29 days in the routine rehabilitation group to 14 days in the home rehabilitation group. Patient satisfaction was in favor of the latter group.\n Early supported discharge with continuity of home rehabilitation services for the majority of moderately disabled stroke patients during the first 3-month period after acute stroke is not less beneficial than routine rehabilitation and can be a rehabilitation service of choice if follow-up at 6 and 12 months confirms the suggested effectiveness and considerable reduction in use of health care.", "Stroke is a complicated disease that requires a multidisciplinary approach for its management. We postulated that variance analysis applied to a stroke pathway, by identifying major problem areas and encouraging timely corrective actions, would lead to more efficient healthcare delivery to hospitalised stroke patients.\n Prospectively collected variance data from consecutive stroke patients discharged from a tertiary hospital in Singapore during a 3-month period in 2000 were used to identify the major variances causing increased length of stay. These were compared and contrasted to variance data collected during the same 3-month period in the subsequent year (2001), after the implementation of stroke pathway and the availability of monthly variance analysis reports. Patient characteristics and outcome measures were also compared between the two study periods.\n The four major variances that accounted for increased length of stay were, in descending order of the number of patients affected, awaiting bed availability in step-down facilities, delay in head computed tomographic scan performance, awaiting family's decision on discharge plan and incomplete application submitted to step-down facilities. After implementation of the stroke pathway with ongoing variance analysis, all four variances showed different extent of improvements. There were no significant differences in patient characteristics between the two study periods, whereas the average length of stay significantly diminished in the late study period with a trend for decreased in-hospital mortality, compared to the early study period.\n Variance analysis applied in the context of a stroke pathway was effective in identifying major variances causing increased length of stay. This allowed targeted intervention to improve efficiency of healthcare delivery to stroke patients.", "To examine the effect of contact with a stroke family care worker on the physical, social, and psychological status of stroke patients and their carers.\n Randomised controlled trial with broad entry criteria and blinded outcome assessment six months after randomisation.\n A well organised stroke service in an Edinburgh teaching hospital.\n 417 patients with an acute stroke in the previous 30 days randomly allocated to be contacted by a stroke family care worker (210) or to receive standard care (207). The patients represented 67% of all stroke patients assessed at the hospital during the study period.\n Patient completed Barthel index, Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, mental adjustment to stroke scale, and patient satisfaction questionnaire; carer completed Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, caregiving bassles scale, and carer satisfaction questionnaire.\n The groups were balanced for all important baseline variables. There were no significant differences in physical outcomes in patients or carers, though patients in the treatment group were possibly more helpless less well adjusted socially, and more depressed, whereas carers in the treatment group were possibly less hassled and anxious. However, both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care, in particular those related to communication and support.\n The introduction of a stroke family care worker improved patients' and their carers' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients' physical wellbeing." ]

[ "16822111", "21924563", "1861939", "17214891", "16893677", "15762903", "14687254", "12399345", "15249261" ]

[ "Internet-based health information consumer skills intervention for people living with HIV/AIDS.", "Adoption, reach and effectiveness of computer-based, practitioner delivered and combined smoking interventions in general medical practices: a three-arm cluster randomized trial.", "Increasing patient knowledge, satisfaction, and involvement: randomized trial of a communication intervention.", "Medical communication and technology: a video-based process study of the use of decision aids in primary care consultations.", "What factors are associated with the integration of evidence retrieval technology into routine general practice settings?", "Can computer-generated evidence-based care suggestions enhance evidence-based management of asthma and chronic obstructive pulmonary disease? A randomized, controlled trial.", "Effects of computerized guidelines for managing heart disease in primary care.", "Effect of computerised evidence based guidelines on management of asthma and angina in adults in primary care: cluster randomised controlled trial.", "Providing a web-based online medical record with electronic communication capabilities to patients with congestive heart failure: randomized trial." ]

[ "Medical information can improve health, and there is an enormous amount of health information available on the Internet. A randomized clinical trial tested the effectiveness of an intervention based on social- cognitive theory to improve information use among people living with HIV/AIDS. Men and women (N = 448) were placed in either (a) an 8-session intervention that focused on Internet information consumer skills or (b) a time-matched support group and were followed to 9 months postintervention. The Internet skills group demonstrated greater Internet use for health, information coping, and social support compared with the control group. The authors conclude that people with HIV infection may benefit from increased access to health information on the Internet and that vulnerability to misinformation and fraud can be reduced through behavioral interventions.\n Copyright 2006 APA, all rights reserved.", "Brief advice for smoking patients has not been sufficiently integrated in routine care. Computer-based interventions emerged as a time saving option that might help to exhaust the potential population impact of the general practice setting.\n 151 practices were randomly assigned to one of three intervention programs consisting in the delivery of: (1) brief advice by the practitioner; (2) individually tailored computer-generated letters; or (3) a combination of both interventions. We assessed three dimensions of population impact: (1) adoption, i.e., the rate of practices participating in the program; (2) reach, measured as the number of interventions provided within 7 months; (3) effectiveness, measured as smoking abstinence at 12-months follow-up.\n Among the practices, 70% adopted the program with no significant differences across study groups. Treatment was provided to 3086 adult smokers. Negative binomial regression analysis revealed that the number of interventions provided was higher in practices allocated to the tailored letter and combination intervention groups by 215% (p<.01) and 127% (p=.02), respectively, compared to the brief advice intervention group. Among the patients who received the combination of both intervention, the odds of point abstinence from smoking was increased by 65% (p=.02) and 32% (p=.01) compared to the brief advice and tailored letters intervention respectively. Comparing the number of abstinent patients at follow-up revealed that the tailored letter and combination interventions were superior to the brief advice intervention.\n Computer-based interventions alone or in addition to conventional practitioner-delivered advice can foster the participation of general medical practices in tobacco control.\n Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.", "A brief educational intervention to promote effective communication between physicians, children, and parents during pediatric office visits was designed and tested. A randomized clinical trial involving 141 children (5- to 15-year-olds) tested the effectiveness of the intervention to improve the process and outcome of medical care. The intervention was contained in three brief videotapes (one each for parents, physicians, and patients) and in accompanying written materials. Materials were designed to build skills and motivation for increased child competence and participation during pediatric medical visits. Control subjects saw health education videotapes and received materials comparable in length with those of experimental subjects. Postintervention medical visit process was analyzed using videotapes of visits. Visit outcomes, assessed with standardized instruments and interviews, included children's rapport with physicians, children's anxiety, children's preference for an active health role, children's recall of information, parents' satisfaction with the medical visit, and physician satisfaction. Results indicated that physicians in the intervention group, compared with their counterparts in the control group, more often included children in discussions of medical recommendations (50% vs 29%, t = 2.39, P less than .05); that children in the intervention group, compared with control children, recalled more medication recommendations (77% vs 47%, P less than .01) and reported greater satisfaction and preference for an active health role; and that the intervention and control groups did not differ in parent satisfaction, physician satisfaction, or child anxiety. The results suggest that a brief educational intervention administered during waiting room time can positively impact physician-child rapport and children's preference for an active role in health and their acquisition of medical information.", "Much of the research on decision-making in health care has focused on consultation outcomes. Less is known about the process by which clinicians and patients come to a treatment decision. This study aimed to quantitatively describe the behaviour shown by doctors and patients during primary care consultations when three types of decision aids were used to promote treatment decision-making in a randomised controlled trial.\n A video-based study set in an efficacy trial which compared the use of paper-based guidelines (control) with two forms of computer-based decision aids (implicit and explicit versions of DARTS II). Treatment decision concerned warfarin anti-coagulation to reduce the risk of stroke in older patients with atrial fibrillation. Twenty nine consultations were video-recorded. A ten-minute 'slice' of the consultation was sampled for detailed content analysis using existing interaction analysis protocols for verbal behaviour and ethological techniques for non-verbal behaviour.\n Median consultation times (quartiles) differed significantly depending on the technology used. Paper-based guidelines took 21 (19-26) minutes to work through compared to 31 (16-41) minutes for the implicit tool; and 44 (39-55) minutes for the explicit tool. In the ten minutes immediately preceding the decision point, GPs dominated the conversation, accounting for 64% (58-66%) of all utterances and this trend was similar across all three arms of the trial. Information-giving was the most frequent activity for both GPs and patients, although GPs did this at twice the rate compared to patients and at higher rates in consultations involving computerised decision aids. GPs' language was highly technically focused and just 7% of their conversation was socio-emotional in content; this was half the socio-emotional content shown by patients (15%). However, frequent head nodding and a close mirroring in the direction of eye-gaze suggested that both parties were active participants in the conversation\n Irrespective of the arm of the trial, both patients' and GPs' behaviour showed that they were reciprocally engaged in these consultations. However, even in consultations aimed at promoting shared decision-making, GPs' were verbally dominant, and they worked primarily as information providers for patients. In addition, computer-based decision aids significantly prolonged the consultations, particularly the later phases. These data suggest that decision aids may not lead to more 'sharing' in treatment decision-making and that, in their current form, they may take too long to negotiate for use in routine primary care.", "Information retrieval systems have the potential to improve patient care but little is known about the variables which influence clinicians' uptake and use of systems in routine work.\n To determine which factors influenced use of an online evidence retrieval system.\n Computer logs and pre- and post-system survey analysis of a 4-week clinical trial of the Quick Clinical online evidence system involving 227 general practitioners across Australia.\n Online evidence use was not linked to general practice training or clinical experience but female clinicians conducted more searches than their male counterparts (mean use=14.38 searches, S.D.=11.68 versus mean use=8.50 searches, S.D.=9.99; t=2.67, d.f.=157, P=0.008). Practice characteristics such as hours worked, type and geographic location of clinic were not associated with search activity. Information seeking was also not related to participants' perceived information needs, computer skills, training nor Internet connection speed. Clinicians who reported direct improvements in patient care as a result of system use had significantly higher rates of system use than other users (mean use=12.55 searches, S.D.=13.18 versus mean use=8.15 searches, S.D.=9.18; t=2.322, d.f.=154 P=0.022). Comparison of participants' views pre- and post- the trial, showed that post-trial clinicians expressed more positive views about searching for information during a consultation (chi(2)=27.40, d.f.=4, P< or =0.001) and a significantly greater number reported seeking information between consultations as a result of having access to an online evidence system in their consulting rooms (chi(2)=9.818, d.f.=2, P=0.010).\n Clinicians' use of an online evidence system was directly related to their reported experiences of improvements in patient care. Post-trial clinicians positively changed their views about having time to search for information and pursued more questions during clinic hours.", "Translation of evidence-based guidelines into clinical practice has been inconsistent. We performed a randomized, controlled trial of guideline-based care suggestions delivered to physicians when writing orders on computer workstations.\n Inner-city academic general internal medicine practice.\n Randomized, controlled trial of 246 physicians (25 percent faculty general internists, 75 percent internal medicine residents) and 20 outpatient pharmacists. We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease. Care suggestions concerning drugs and monitoring were delivered to a random half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations. A 2 x 2 factorial randomization of practice sessions and pharmacists resulted in four groups of patients: physician intervention, pharmacist intervention, both interventions, and controls. DATA EXTRACTION/COLLECTION METHODS: Adherence to the guidelines and clinical activity was assessed using patients' electronic medical records. Health-related quality of life, medication adherence, and satisfaction with care were assessed using telephone questionnaires.\n During their year in the study, patients made an average of five scheduled primary care visits. There were no differences between groups in adherence to the care suggestions, generic or condition-specific quality of life, satisfaction with physicians or pharmacists, medication compliance, emergency department visits, or hospitalizations. Physicians receiving the intervention had significantly higher total health care costs. Physician attitudes toward guidelines were mixed.\n Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease.", "Electronic information systems have been proposed as one means to reduce medical errors of commission (doing the wrong thing) and omission (not providing indicated care).\n To assess the effects of computer-based cardiac care suggestions.\n A randomized, controlled trial targeting primary care physicians and pharmacists.\n A total of 706 outpatients with heart failure and/or ischemic heart disease.\n Evidence-based cardiac care suggestions, approved by a panel of local cardiologists and general internists, were displayed to physicians and pharmacists as they cared for enrolled patients.\n Adherence with the care suggestions, generic and condition-specific quality of life, acute exacerbations of their cardiac disease, medication compliance, health care costs, satisfaction with care, and physicians' attitudes toward guidelines.\n Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions. The intervention had no effect on physicians' adherence to the care suggestions (23% for intervention patients vs 22% for controls). There were no intervention-control differences in quality of life, medication compliance, health care utilization, costs, or satisfaction with care. Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients.\n Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease. Future studies must weigh the benefits and costs of different (and perhaps more Draconian) methods of affecting clinician behavior.", "To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care.\n A before and after pragmatic cluster randomised controlled trial utilising a two by two incomplete block design. Setting: 60 general practices in north east England.\n General practitioners and practice nurses in the study practices and their patients aged 18 or over with angina or asthma.\n Adherence to the guidelines, based on review of case notes and patient reported generic and condition specific outcome measures.\n The computerised decision support system had no significant effect on consultation rates, process of care measures (including prescribing), or any patient reported outcomes for either condition. Levels of use of the software were low.\n No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care. This was probably due to low levels of use of the software, despite the system being optimised as far as was technically possible. Even if the technical problems of producing a system that fully supports the management of chronic disease were solved, there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex, multiple conditions.", "It is possible to provide patients with secure access to their medical records using the Internet. Such access may assist patients in the self-management of chronic diseases such as heart failure.\n To assess how a patient-accessible online medical record affects patient care and clinic operations. The SPPARO (System Providing Access to Records Online) software consisted of a web-based electronic medical record, an educational guide, and a messaging system enabling electronic communication between the patient and staff.\n A randomized controlled trial was conducted in a specialty practice for patients with heart failure. Surveys assessing doctor-patient communication, adherence, and health status were conducted at baseline, 6 months, and 1 year. Use of the system, message volume, utilization of clinical services, and mortality were monitored.\n One hundred and seven patients were enrolled (54 intervention and 53 controls). At 12 months, the intervention group was not found to be superior in self-efficacy (KCCQ self-efficacy score 91 vs. 85, p=0.08), but was superior in general adherence (MOS compliance score 85 vs. 78, p=0.01). A trend was observed for better satisfaction with doctor-patient communication. The intervention group had more emergency department visits (20 vs. 8, p=0.03), but these visits were not temporally related to use of the online medical record. There were no adverse effects from use of the system.\n Providing patients with congestive heart failure access to an online medical record was feasible and improved adherence. An effect on health status could not be demonstrated in this pilot study." ]

[ "15774341", "15484202", "17785708", "7937251", "11879296", "11157015", "9243585", "18490891", "17470863" ]

[ "A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment.", "Exercise manages fatigue during breast cancer treatment: a randomized controlled trial.", "Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.", "A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy.", "Fatigue and quality of life outcomes of exercise during cancer treatment.", "Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial.", "Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer.", "A brief intervention for fatigue management in breast cancer survivors.", "Randomized trial of exercise therapy in women treated for breast cancer." ]

[ "This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy. The study was designed as a randomised controlled trial (RCT). Physical functioning, fatigue and Quality of Life (QoL) outcomes were evaluated pre and post a 12-week intervention. The results showed that after 12 weeks the women who participated in the exercise programme (n = 12) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls (n = 10). Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance. These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe, well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer. Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women. Future studies need to address these issues and determine if these short-term benefits can be sustained.", "Fatigue is the most prevalent and debilitating symptom experienced by breast cancer patients receiving adjuvant chemotherapy or radiation therapy and few evidence-based treatments are available to manage this distressing side-effect. The purpose of this multi-institutional randomized controlled trial was to determine the effects of exercise on fatigue levels during treatment for breast cancer. Sedentary women (N=119) with Stage 0-III breast cancer receiving outpatient adjuvant chemotherapy or radiation therapy were randomized to a home-based moderate-intensity walking exercise program or to usual care for the duration of their cancer treatment. Of participants randomized to exercise, 72% adhered to the exercise prescription; 61% of the usual care group adhered. The intention-to-treat analysis revealed no group differences in part because of a dilution of treatment effect as 39% of the usual care group exercised and 28% of the exercise group did not. When exercise participation was considered using the data analysis method of instrumental variables with principal stratification, a clinically important and statistically significant (p=0.03) effect of exercise on pretest-to-posttest change in fatigue levels was demonstrated. Adherence to a home-based moderate-intensity walking exercise program may effectively mitigate the high levels of fatigue prevalent during cancer treatment.", "Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects.\n We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema.\n The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem (P = .015), aerobic fitness (P = .006), and percent body fat (adjusted P = .076). Resistance exercise was superior to usual care for improving self-esteem (P = .018), muscular strength (P < .001), lean body mass (P = .015), and chemotherapy completion rate (P = .033). Changes in cancer-specific QOL, fatigue, depression, and anxiety favored the exercise groups but did not reach statistical significance. Exercise did not cause lymphedema or adverse events.\n Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy, but they did improve self-esteem, physical fitness, body composition, and chemotherapy completion rate without causing lymphedema or significant adverse events.", "To examine the effects of a comprehensive rehabilitation program on facilitating physical and psychosocial adaptation of women with breast cancer who are receiving adjuvant chemotherapy.\n Experimental.\n Breast evaluation clinics of two New England medical centers with comprehensive cancer treatment programs.\n 14 women (mean age = 44 years) receiving adjuvant chemotherapy for breast cancer (86% stage II) following surgical treatment.\n Subjects were assigned randomly to the experimental group or the usual care group. Experimental group members began a structured exercise program of walking and attended support group meetings. All subjects were tested before beginning chemotherapy, during the course of chemotherapy, and one month following chemotherapy completion.\n Performance status, physical functioning, psychosocial adjustment, self-concept and body image, and 12 symptoms (e.g., fatigue, nausea, anxiety).\n Measures of physical performance, psychosocial adjustment, and symptom intensity revealed improved adaptation in subjects who completed the walking/support group program.\n Physical and psychosocial benefits from a modest walking exercise program and a support group are possible for patients receiving adjuvant chemotherapy.\n Although more detailed research is necessary to answer some of the questions raised by this study, implementing the walking program and forming a support group are achievable in an outpatient setting.", "Despite the recognition of fatigue as a common and distressing symptom during cancer treatment, there are few evidence-based interventions available to manage such fatigue. The purpose of this multi-institutional pilot study was to explore the effects of a home-based moderate walking exercise intervention on fatigue, physical functioning, emotional distress, and quality of life (QOL) during breast cancer treatment.\n Fifty-two women were recruited from five university hospital outpatient departments for this pilot study with an experimental design. Subjects were randomly assigned to the walking program or to usual care during adjuvant chemotherapy or radiation therapy for breast cancer. Symptoms, physical functioning, and QOL were measured at baseline, midtreatment, and at the end of treatment.\n Women who exercised at least 90 minutes per week on 3 or more days reported significantly less fatigue and emotional distress as well as higher functional ability and QOL than women who were less active during treatment.\n A home-based walking exercise program is a potentially effective, low-cost, and safe intervention to manage fatigue and to improve QOL during adjuvant chemotherapy or radiation therapy for breast cancer. This health-promoting self-care activity needs further testing in large randomized clinical trials.", "Self-directed and supervised exercise were compared with usual care in a clinical trial designed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer.\n One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life, aerobic capacity, and body weight. Participants were randomly allocated to one of three intervention groups: usual care (control group), self-directed exercise, or supervised exercise. Quality of life, aerobic capacity, and body weight measures were repeated at 26 weeks. The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks.\n Physical functioning in the control group decreased by 4.1 points, whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups, respectively (P =.04). Post hoc analysis showed a moderately large (and clinically important) difference between the self-directed and control groups (9.8 points; P =.01) and a more modest difference between the supervised and control groups (6.3 points; P =.09). No significant differences between groups were observed for changes in quality of life scores. In a secondary analysis of participants stratified by type of adjuvant therapy, supervised exercise improved aerobic capacity (+3.5 mL/kg/min; P =.01) and reduced body weight (-4.8 kg; P <.05) compared with usual care only in participants not receiving chemotherapy.\n Physical exercise can blunt some of the negative side effects of breast cancer treatment, including reduced physical functioning. Self-directed exercise is an effective way to improve physical functioning compared with usual care. In participants not receiving chemotherapy, supervised exercise may increase aerobic capacity and reduce body weight compared with usual care.", "PURPOSES/OBJECTIVES: To test the hypothesis that women participating in a walking exercise program during radiation therapy treatment for breast cancer would demonstrate more adaptive responses as evidenced by higher levels of physical functioning and lower levels of symptom intensity than women who did not participate.\n Experimental, two-group pretest, post-test.\n Two university teaching hospital outpatient radiation therapy departments.\n 46 women beginning a six-week program of radiation therapy for early stage breast cancer.\n Following random assignment, subjects in the exercise group maintained an individualized, self-paced, home-based walking exercise program throughout treatment. The control group received usual care. Dependent variables were measured prior to and at the end of radiation therapy. In addition, symptoms were assessed at the end of three weeks of treatment.\n Participation in the walking exercise program, physical functioning fatigue, emotional distress, and difficulty sleeping.\n Hypothesis testing by multivariate analysis of covariance, with pretest scores as covariates, indicated significant differences between groups on outcome measures (p < 0.001). The exercise group scored significantly higher than the usual care group on physical functioning (p = 0.003) and symptom intensity, particularly fatigue, anxiety, and difficulty sleeping. Fatigue was the most frequent and intense subjective symptom reported.\n A self-paced, home-based walking exercise program can help manage symptoms and improve physical functioning during radiation therapy.\n Nurse-prescribed and -monitored exercise is an effective, convenient, and low-cost self-care activity that reduces symptoms and facilitates adaptation to breast cancer diagnosis and treatment.", "The purpose of this randomized control trial was to verify the effectiveness of a brief group intervention that combines stress management psycho-education and physical activity (ie, independent variable) intervention in reducing fatigue and improving energy level, quality of life (mental and physical), fitness (VO 2submax), and emotional distress (ie, dependent variables) in breast cancer survivors. This study applied Lazarus and Folkman stress-coping theoretical framework, as well as Salmon's unifying theory of physical activity. Eighty-seven French-speaking women who had completed their treatments for nonmetastatic breast cancer at a university hospital in Quebec City, Canada, were randomly assigned to either the group intervention (experimental) or the usual-care (control) condition. Data were collected at baseline, postintervention, and at 3-month follow-up. The 4-week group intervention was cofacilitated by 2 nurses. Results showed that participants in the intervention group showed greater improvement in fatigue, energy level, and emotional distress at 3-month follow-up, and physical quality of life at postintervention, compared with the participants in the control group. These results suggest that a brief psycho-educational group intervention focusing on active coping strategies and physical activity is beneficial to cancer survivors after breast cancer treatments.", "To examine the effects of aerobic exercise therapy on quality of life (QoL) and associated outcomes in women treated for breast cancer. Evidence suggests that exercise may be beneficial, but no trial has included an exercise-placebo and a usual-care group to control for the attention effects that might be associated with aerobic exercise interventions in cancer patients.\n A total of 108 women who had been treated for breast cancer 12 to 36 months previously were randomly assigned to supervised aerobic exercise therapy (n = 34), exercise-placebo (body conditioning; n = 36), or usual care (n = 38). Exercise therapy and exercise-placebo sessions took place three times per week for 8 weeks. Outcomes included QoL, depression, exercise behavior, aerobic fitness; outcomes were assessed at baseline and at the 8- and 24-week follow-up.\n Analyses of covariance revealed a significant mean difference of 9.8 units in Functional Assessment of Cancer Therapy-General (primary outcome) favoring aerobic exercise therapy at 8 weeks, relative to usual care. Significant differences that favored aerobic exercise therapy relative to usual care were recorded for Functional Assessment of Cancer Therapy-Breast, social/family well-being, functional well-being, and breast cancer subscale scores at 8-week follow-up. Psychological health outcomes improved modestly for both intervention groups; these improvements were sustained for several end points.\n Exercise therapy had large, clinically meaningful, short-term beneficial effects on QoL in women treated for breast cancer; this finding cannot be attributable to attention, given that the exercise-placebo group did not report similar effects relative to usual care." ]

[ "18667099", "9210279", "17364418", "11037083", "19182178", "10077290", "12668405", "16551154", "10883563" ]

[ "Cognitive behaviour therapy for violent men with antisocial personality disorder in the community: an exploratory randomized controlled trial.", "Feminist-cognitive-behavioral and process-psychodynamic treatments for men who batter: interaction of abuser traits and treatment models.", "A cognitive behavioral therapy for alcohol-dependent domestic violence offenders: an integrated substance abuse-domestic violence treatment approach (SADV).", "Randomized controlled trial of cognitive behaviour therapy for repeated consultations for medically unexplained complaints: a feasibility study in Sri Lanka.", "Cognitive-behavioural therapy v. social activity therapy for people with psychosis and a history of violence: randomised controlled trial.", "Manual-assisted cognitive-behaviour therapy (MACT): a randomized controlled trial of a brief intervention with bibliotherapy in the treatment of recurrent deliberate self-harm.", "Tayside-Fife clinical trial of cognitive-behavioural therapy for medication-resistant psychotic symptoms. Results to 3-month follow-up.", "Cognitive-behavioral therapy for women with lifelong vaginismus: a randomized waiting-list controlled trial of efficacy.", "The San Diego Navy experiment: an assessment of interventions for men who assault their wives." ]

[ "Little information exists on treatment effectiveness in antisocial personality disorder (ASPD). We investigated the feasibility and effectiveness of carrying out a randomized controlled trial of cognitive behaviour therapy (CBT) in men with ASPD who were aggressive.\n This was an exploratory two-centre, randomized controlled trial in a community setting. Fifty-two adult men with a diagnosis of ASPD, with acts of aggression in the 6 months prior to the study, were randomized to either treatment as usual (TAU) plus CBT, or usual treatment alone. Change over 12 months of follow-up was assessed in the occurrence of any act of aggression and also in terms of alcohol misuse, mental state, beliefs and social functioning.\n The follow-up rate was 79%. At 12 months, both groups reported a decrease in the occurrence of any acts of verbal or physical aggression. Trends in the data, in favour of CBT, were noted for problematic drinking, social functioning and beliefs about others.\n CBT did not improve outcomes more than usual treatment for men with ASPD who are aggressive and living in the community in this exploratory study. However, the data suggest that a larger study is required to fully assess the effectiveness of CBT in reducing aggression, alcohol misuse and improving social functioning and view of others. It is feasible to carry out a rigorous randomized controlled trial in this group.", "At a community-based domestic violence program, 218 men with a history of partner abuse were randomly assigned to either feminist-cognitive-behavioral or process-psychodynamic group treatments. The treatments were not hypothesized to differ in outcome. However, men with particular characteristics were expected to have lower recidivism rates depending on the type of treatment received. Treatment integrity was verified through audio-taped codings of each session. The partners of 79% of the 136 treatment completers gave reports of the men's behavior an average of 2 years post-treatment. These reports were supplemented with arrest records and self-reports. Rates of violence did not differ significantly between the two types of treatment nor did reports from the women of their fear level, general changes perceived in the men, and conflict resolution methods. However, interaction effects were found between some offender traits and the two treatments. As predicted, men with dependent personalities had better outcomes in the process-psychodynamic groups and those with antisocial traits had better outcomes in the cognitive-behavioral groups. The results suggest that more effective treatment may occur if it is tailored to specific characteristics of offenders.", "This pilot study evaluated the efficacy of a twelve-session cognitive behavioral group therapy for alcohol-dependent males with co-occurring interpersonal violence (IPV). Participants were 85 alcohol-dependent males who were arrested for domestic violence within the past year. Seventy-eight male adults were randomized to either a cognitive behavioral Substance Abuse Domestic Violence (SADV) group (N = 40) or a Twelve-Step Facilitation (TSF) Group (N = 38). There was no significant difference between SADV versus TSF in the number of sessions attended. Regarding substance use, the group assigned to SADV reported using alcohol significantly fewer days (eg, 90 days of abstinence across the 12 weeks of treatment) as compared to the TSF group. Regarding physical violence, there was a trend for participants in the SADV condition to achieve a greater reduction in the frequency of violent episodes across time compared to individuals in the TSF group. These data suggest the promise of the SADV group therapy approach for alcohol-dependent males with a history of IPV who present for substance abuse treatment.", "Research on the management and the outcome of treatment of medically unexplained symptoms is very limited. Development of simple but effective techniques for treatment and demonstration of their effectiveness when applied in primary health care are needed.\n A randomized controlled trial was carried out with follow-up assessments at 3 months after baseline assessments using the Short Explanatory Model Interview (SEMI), General Health Questionnaire (GHQ-30), Bradford Somatic Inventory (BSI) and patient satisfaction on a visual analogue scale. The study was carried out in a general out-patient clinic in Sri Lanka. The intervention group received six, 30 min sessions based on the principles of cognitive behavioural therapy over a period of 3 months. The control group received standard clinical care.\n Eighty patients out of the 110 patients referred, were eligible. Sixty-eight were randomly allocated equally to the control and treatment groups. All 34 in the treatment group accepted the treatment offer and 22 completed between three and six sessions. At 3 months, 24 in the treatment and 21 in the control group completed follow-up assessments. Intention-to-treat analysis revealed significant differences in mean scores of outcome measures (adjusted for baseline scores) between control and intervention groups respectively--complaints 6.1 and 3.8 (P = 0.001), GHQ 10.4 and 6.3 (P = 0.04), BSI score 15.6 and 132 (P < 0-01), visits 7.9 and 3.1 (P = 0.004).\n Intervention based on cognitive behavioural therapy is feasible and acceptable to patients with medically unexplained symptoms from a general out-patients clinic in Sri Lanka. It had a significant effective in reducing symptoms, visits and distress, and in increasing patient satisfaction.", "Aggression and violence are serious problems in schizophrenia. Cognitive-behavioural therapy (CBT) has been shown to be an effective treatment for psychosis although there have been no studies to date evaluating the impact of CBT for people with psychosis and a history of violence.\n To investigate the effectiveness of CBT on violence, anger, psychosis and risk outcomes with people who had a diagnosis of schizophrenia and a history of violence.\n This was a single-blind randomised controlled trial of CBT v. social activity therapy (SAT) with a primary outcome of violence and secondary outcomes of anger, symptoms, functioning and risk. Outcomes were evaluated by masked assessors at 6 and 12 months (trial registration: NRR NO50087441).\n Significant benefits were shown for CBT compared with control over the intervention and follow-up period on violence, delusions and risk management.\n Cognitive-behavioural therapy targeted at psychosis and anger may be an effective treatment for reducing the occurrence of violence and further investigation of its benefits is warranted.", "The treatment of deliberate self-harm (parasuicide) remains limited in efficacy. Despite a range of psychosocial, educational and pharmacological interventions only one approach, dialectical behaviour therapy, a form of cognitive-behaviour therapy (CBT), has been shown to reduce repeat episodes, but this is lengthy and intensive and difficult to extrapolate to busy clinical practice. We investigated the effectiveness of a new manual-based treatment varying from bibliotherapy (six self-help booklets) alone to six sessions of cognitive therapy linked to the booklets, which contained elements of dialectical behaviour therapy.\n Thirty-four patients, aged between 16 and 50, seen after an episode of deliberate self-harm, with personality disturbance within the flamboyant cluster and a previous parasuicide episode within the past 12 months, were randomly assigned to treatment with manual-assisted cognitive-behaviour therapy (MACT N = 18) or treatment as usual (TAU N = 16). Assessment of clinical symptoms and social function were made at baseline and repeated by an independent assessor masked to treatment allocation at 6 months. The number and rate of all parasuicide attempts, time to next episode and costs of care were also determined.\n Thirty-two patients (18 MACT; 14 TAU) were seen at follow-up and 10 patients in each group (56% MACT and 71% TAU) had a suicidal act during the 6 months. The rate of suicidal acts per month was lower with MACT (median 0.17/month MACT; 0.37/month TAU; P = 0.11) and self-rated depressive symptoms also improved (P = 0.03). The treatment involved a mean of 2.7 sessions and the observed average cost of care was 46% less with MACT (P = 0.22).\n Although limited by the small sample, the results of this pilot study suggest that this new form of cognitive-behaviour therapy is promising in its efficacy and feasible in clinical practice.", "Evidence for the efficacy of cognitive-behavioural therapy for schizophrenia is promising but evidence for clinical effectiveness is limited.\n To test the effectiveness of cognitive-behavioural therapy delivered by clinical nurse specialists in routine practice.\n Of 274 referrals, 66 were allocated randomly to 9 months of treatment as usual (TAU), cognitive-behavioural therapy plus TAU (CBT) or supportive psychotherapy plus TAU (SPT) and followed up for 3 months.\n Treatment effects were modest but the CBT condition gave significantly greater improvement in overall symptom severity than the SPT or TAU conditions combined (F (1,53)=4.14; P=0.05). Both the CBT and SPT conditions combined gave significantly greater improvement in severity of delusions than did the TAU condition (F (1,53)=4.83; P=0.03). Clinically significant improvements were achieved by 7/21 in the CBT condition (33%), 3/19 in the SPT condition (16%) and 2/17 in the TAU condition (12%).\n Cognitive-behavioural therapy delivered by clinical nurse specialists is a helpful adjunct to routine care for some people with chronic psychosis.", "Women with lifelong vaginismus (N=117) were randomly assigned to cognitive-behavioral group therapy, cognitive-behavioral bibliotherapy, or a waiting list. Manualized treatment comprised sexual education, relaxation exercises, gradual exposure, cognitive therapy, and sensate focus therapy. Group therapy consisted of ten 2-hr sessions with 6 to 9 participants per group. Assistance with minimal-contact bibliotherapy consisted of 6 biweekly, 15-min telephone contacts. Twenty-one percent of the participants left the study before posttreatment assessment. Intent-to-treat analysis revealed that successful intercourse at posttreatment was reported by 14% of the treated participants compared with none of the participants in the control condition. At the 12-month follow-up 21% of the group therapy participants and 15% of the bibliotherapy participants, respectively, reported successful intercourse. Cognitive-behavioral treatment of lifelong vaginismus was thus found to be efficacious, but the small effect size of the treatment warrants future efforts to improve the treatment.\n Copyright (c) 2006 APA, all rights reserved.", "Three different 12-month interventions for servicemen who had been substantiated as having physically assaulted their wives were used and the outcomes examined. The 861 couples of the study were randomly assigned to 4 groups: a men's group, a conjoint group, a rigorously monitored group, and a control group. Cognitive-behavioral interventions were implemented for the men's and conjoint groups, and outcome data were gathered from male perpetrators and female victims at roughly 6-month intervals over the approximately 18-month experimental period. Data analyses revealed nonsignificant differences between the experimental groups over a variety of outcome measures." ]

[ "18055007", "15919846", "18155287", "8732700", "6437150", "8559961", "3302144", "18227359", "9803696" ]

[ "Transtheoretical model-based multiple behavior intervention for weight management: effectiveness on a population basis.", "Transtheoretical model-chronic disease care for obesity in primary care: a randomized trial.", "Initial efficacy of MI, TTM tailoring and HRI's with multiple behaviors for employee health promotion.", "Effectiveness of a behavioral weight control program for blacks and whites with NIDDM.", "Minimal interventions for weight control: a cost-effective alternative.", "Physical activity within a community-based weight control program: program evaluation and predictors of success.", "Effects of diet and exercise interventions on control and quality of life in non-insulin-dependent diabetes mellitus.", "Clinic-based support to help overweight patients with type 2 diabetes increase physical activity and lose weight.", "Use of personal trainers and financial incentives to increase exercise in a behavioral weight-loss program." ]

[ "The increasing prevalence of overweight and obesity underscores the need for evidence-based, easily disseminable interventions for weight management that can be delivered on a population basis. The Transtheoretical Model (TTM) offers a promising theoretical framework for multiple behavior weight management interventions.\n Overweight or obese adults (BMI 25-39.9; n=1277) were randomized to no-treatment control or home-based, stage-matched multiple behavior interventions for up to three behaviors related to weight management at 0, 3, 6, and 9 months. All participants were re-assessed at 6, 12, and 24 months.\n Significant treatment effects were found for healthy eating (47.5% versus 34.3%), exercise (44.90% versus 38.10%), managing emotional distress (49.7% versus 30.30%), and untreated fruit and vegetable intake (48.5% versus 39.0%) progressing to Action/Maintenance at 24 months. The groups differed on weight lost at 24 months. Co-variation of behavior change occurred and was much more pronounced in the treatment group, where individuals progressing to Action/Maintenance for a single behavior were 2.5-5 times more likely to make progress on another behavior. The impact of the multiple behavior intervention was more than three times that of single behavior interventions.\n This study demonstrates the ability of TTM-based tailored feedback to improve healthy eating, exercise, managing emotional distress, and weight on a population basis. The treatment produced a high level of population impact that future multiple behavior interventions can seek to surpass.", "To compare health benefits achieved in a transtheoretical model-chronic disease (TM-CD) minimal intervention for obesity vs. augmented usual care (AUC). Research Method and Procedures: This was a 2-year, randomized clinical trial with overweight or obese men and women from 15 primary care sites. AUC (n = 336) included dietary and exercise advice, prescriptions, and three 24-hour dietary recalls every 6 months. TM-CD care (n = 329) included AUC elements plus \"stage of change\" (SOC) assessments for five target behaviors every other month, mailed SOC and target behavior-matched workbooks, and monthly telephone calls from a weight-loss advisor. Weight change was the primary outcome.\n Repeated measures models under the missing at random assumption yielded nonsignificant adjusted differences between the AUC and TM-CD groups for weight change, waist circumference, energy intake or expenditure, blood pressure, and blood lipids. The pattern of change over time suggested that TM-CD participants were trying harder to impact target behaviors during the first 6 to 12 months of the trial but relapsed afterward. Sixty percent of trial participants maintained their baseline weights for 18 to 24 months.\n A combination of mailed patient materials and monthly telephone calls based on the transtheoretical model and some elements of chronic disease care is not powerful enough, relative to AUC, to alter target behaviors among overweight primary care patients in an obesogenic environment. AUC may be sufficient to maintain weights among at-risk primary care patients.", "This study was designed to compare the initial efficacy of Motivational Interviewing (MI), Online Transtheoretical Model (TTM)-tailored communications and a brief Health Risk Intervention (HRI) on four health risk factors (inactivity, BMI, stress and smoking) in a worksite sample.\n A randomized clinical trial assigned employees to one of three recruitment strategies and one of the three treatments. The treatment protocol included an HRI session for everyone and in addition either a recommended three TTM online sessions or three MI in person or telephone sessions over 6 months. At the initial post-treatment assessment at 6 months, groups were compared on the percentage who had progressed from at risk to taking effective action on each of the four risks.\n Compared to the HRI only group, the MI and TTM groups had significantly more participants in the Action stage for exercise and effective stress management and significantly fewer risk behaviors at 6 months. MI and TTM group outcomes were not different.\n This was the first study to demonstrate that MI and online TTM could produce significant multiple behavior changes. Future research will examine the long-term impacts of each treatment, their cost effectiveness, effects on productivity and quality of life and process variables mediating outcomes.", "To compare the weight losses of black and white patients with NIDDM treated in a year-long behavioral weight loss program.\n Subjects were randomly assigned to a behavioral program that either used a low-calorie diet throughout or included two 12-week periods of a very-low calorie diet (VLCD). Weight, dietary intake, and exercise were measured at 0, 6, and 12 months of treatment, and attendance and self-monitoring records were assessed weekly throughout the year.\n Blacks had smaller weight losses than whites regardless of treatment condition. Overall weight losses (baseline to 1 year) were 7.1 kg in blacks vs 13.9 kg in whites. The differences in overall outcome resulted primarily from greater weight regain in blacks during months 6-12 than in whites. There was a trend for blacks to have poorer attendance than whites during the latter half of the program and for blacks to report smaller changes in calorie intake from baseline to 6 months.\n The results confirm prior studies with nondiabetic patients showing smaller weight losses in blacks than in whites and suggest that these differences may result primarily from faster weight regain in blacks. Further research is needed to more carefully examine the variables that may explain this difference and to develop more effective programs for blacks with NIDDM.", "Two studies were conducted to evaluate simpler, less intensive interventions for weight control which presumably would be more cost-effective and efficient than a \"full-length\" behavioral treatment program. In Study 1, participants in a minimal intervention (MI1) program who attended no regularly scheduled meetings and initially only received three simple verbal instructions about how to lose weight, lost an average of 11.1 lb. by 7-month follow-up. Subjects in three variations of a shortened, less intensive, 6-week behavioral weight loss program lost 7.8, 6.5 and 6.3 lb. but did not significantly differ from MI1 subjects in the amount of weight lost. In Study 2, MI2 subjects lost 5.5 lb. compared to subjects in two variations of a full-length program who lost 8.1 and 11.1 lb. by 6-month follow-up. Again, none of the groups significantly differed from each other in the amount lost. It was concluded that a minimal intervention program seems to produce weight loss and to be a cost-effective and efficient method for some subjects. The difference between the two minimal intervention programs may be related to the payment of a monetary deposit; a model for future research was presented to investigate simpler, less intensive interventions in combination with more complex ones in a \"stepped-care\" fashion.", "To assess the feasibility and effectiveness of adding physical activity sessions to a weight control program in a community health center and to identify individuals suitable for outpatient group treatment with and without physical activity.\n The study population included 42 overweight women who were randomly divided into treatment groups. Both treatment groups received guidance in nutrition and behavior modification and the exercise group also participated in physical activity sessions. Both treatments included 20 sessions and participants were followed up for eight months.\n In both treatments, significant improvements were seen in physical fitness, anthropometric measurements, nutritional knowledge, food consumption, and eating behaviors. Weight loss following three months of weekly sessions did not differ by treatment group. At follow-up there was a trend towards increased maintenance of weight loss in the exercise group, however differences were not statistically significant. Attrition rates were low in both treatments and participant satisfaction was high. Lower baseline BMI predicted larger weight losses, in particular in the exercise group. Other predictors of weight loss included poorer baseline eating behaviors and employment outside of the home. Perceived spouse support predicted continual participation.", "Evidence suggests that diet and exercise are associated with improved glucose tolerance for patients with non-insulin-dependent diabetes mellitus (NIDDM). Seventy-six volunteer adult patients with NIDDM were each assigned to one of four programs: diet, exercise, diet plus exercise, or education (control). Each program required ten weekly meetings. Detailed evaluations were completed prior to the program and after three, six, 12, and 18 months. Evaluations included various psychosocial measures, measures of the quality of life, and fasting blood glucose, glycosylated hemoglobin, and relative weight determinations. Of the 76 original participants, 70 completed the 18-month follow-up study. At 18 months, the combination diet-and-exercise group had achieved the greatest reductions in glycosylated hemoglobin measures. In addition, this group showed significant improvements on a general quality of life measure. These improvements were largely uncorrelated with changes in weight. The authors conclude that the combination of dietary change and physical conditioning benefits NIDDM patients, and that the benefits may be independent of substantial weight loss.", "Our objective was to test the effect of physicians providing brief health lifestyle counseling to patients with type 2 diabetes mellitus during usual care visits.\n We conducted a randomized controlled trial of a 12-month intervention at 2 large community health centers, enrolling 310 patients with a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater. In the intervention group, self-management goals for nutrition and physical activity were set using a tailored computer program. Goals were then reviewed at each clinic visit by physicians. The control group received only printed health education materials. The main outcome measures included change in physical activity and body weight.\n In the intervention group, recommended levels of physical activity increased from 26% at baseline to 53% at 12 months (P< .001) compared with controls (30% to 37%; P= .27), and 32% of patients in the intervention group lost 6 or more pounds at 12 months compared with 18.9% of controls (odds ratio, 2.2; P= .006).\n A brief intervention to increase the dialogue between patients and health care providers about behavioral goals can lead to increased physical activity and weight loss.", "Exercise is the best predictor of long-term weight loss. This study evaluated two strategies for improving exercise adherence and long-term weight loss in obese outpatients. Obese men and women (N = 193) were randomized to 1 of 5 treatment groups for 18 months: standard behavior therapy (SBT); SBT with supervised walks (SW) 3 times per week; SBT + SW with personal trainers (PT), who walked with participants, made phone reminders, and did make-up SW; SBT + SW with monetary incentives (I) for completing SW; and SBT + SW + PT + I. Both PT and I enhanced attendance at SWs, the combination producing the best adherence. Increased walk attendance did not result in higher overall energy expenditure, however, and long-term weight loss was also not improved. Post hoc analyses suggest that the level of exercise needed for successful long-term weight loss is much higher than that usually recommended in behavioral treatment programs." ]

[ "16640064", "17662757", "3896355", "20424590", "19614962", "7841897", "17684661", "18202212", "10753321" ]

[ "Outcomes of clinical trial: tinnitus masking versus tinnitus retraining therapy.", "Use of a self-help book with weekly therapist contact to reduce tinnitus distress: a randomized controlled trial.", "A clinical study of tinnitus maskers.", "Efficacy of repetitive transcranial magnetic stimulation for the treatment of refractory chronic tinnitus: a randomized, placebo controlled study.", "Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study.", "An experimental evaluation of the effects of transcutaneous nerve stimulation (TNS) and applied relaxation (AR) on hearing ability, tinnitus and dizziness in patients with Menière's disease.", "Tinnitus treatment with Trazodone.", "Effect of daily repetitive transcranial magnetic stimulation for treatment of tinnitus: comparison of different stimulus frequencies.", "Idiopathic Subjective Tinnitus Treated by Amitriptyline Hydrochloride/Biofeedback." ]

[ "A controlled clinical study was conducted to evaluate prospectively the clinical efficacy of tinnitus masking (TM) and tinnitus retraining therapy (TRT) in military veterans having clinically significant tinnitus. Qualifying patients were placed into the two groups in an alternating manner (to avoid selection bias), and treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of treatment were evaluated using three self-administered tinnitus questionnaires (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index) and the verbally administered TRT interview forms. Findings are presented from the three written questionnaires, and from two of the interview questions (percentage time aware of, and annoyed by, tinnitus). Outcomes were analyzed on an intent-to-treat basis, using a multilevel modeling approach. Of the 123 patients enrolled, 118 were included in the analysis. Both groups showed significant declines (improvements) on these measures, with the TRT decline being significantly greater than for TM. The greater declines in TRT compared to TM occurred most strongly in patients who began treatment with a \"very big\" tinnitus problem. When patients began treatment with a \"moderate\" tinnitus problem, the benefits of TRT compared to TM were more modest.", "Tinnitus distress can be reduced by means of cognitive-behavior therapy (CBT). To compensate for the shortage of CBT therapists, we aimed, in this study, to investigate the effects of a CBT-based self-help book guided by brief telephone support.\n Seventy-two patients were randomized either to a self-help book and seven weekly phone calls or to a wait-list control condition, later on receiving the self-help book with less therapist support. The dropout rate was 7%. Follow-up data 1 year after completion of treatment were also collected (12% dropout). The Tinnitus Reaction Questionnaire (TRQ) was the main outcome measure, complemented with daily ratings of tinnitus and measures of insomnia, anxiety, and depression.\n On the TRQ, significant reductions were found in the treatment group both immediately following treatment and at 1-year follow-up. In the treatment group, 32% reached the criteria for clinical significance (at least 50% reduction of the TRQ) compared to 5% in the wait-list group. Directly after treatment, two out of five measures showed significant differences in favor of the treatment with more therapist support compared with the group who, after their waiting period, received little therapist support. The self-help treatment was estimated to be 2.6 (seven phone calls) and 4.8 (one phone call) times as cost-effective as regular CBT group treatment.\n Guided self-help can serve as an alternative way to administer CBT for tinnitus. Preliminary results cast some doubts on the importance of weekly therapist contact. The effect size was somewhat smaller than for regular CBT, but on the other hand, the self-help seems far more cost-effective. Future studies should compare treatment modalities directly and explore cost-effectiveness more thoroughly.", "This report describes a three-centre study of the effectiveness of tinnitus maskers, combination instruments (masker plus hearing aid), and hearing aids in the management of tinnitus. Some 472 patients entered the study with 382 reaching the first evaluation session after a minimum period of 6 months from fitting, and 206 reaching the second evaluation not less than 6 months after the first. The study included two control groups, by which to assess the comparative benefit to be derived solely from the investigation and counselling of such patients. The principal results were as follows: thorough investigation and careful counselling do much to help the patient; much further benefit is given by tinnitus masking instruments of various kinds; maskers are more often effective than hearing aids, although the latter are frequently the most appropriate first treatment of those patients who have substantial (but not yet treated or insufficiently treated) hearing difficulties as well; there is no evidence of masking having any harmful effect on hearing. None of the audiometric or tinnitus tests currently employed can be regarded as predictive, either of tinnitus severity, or of the eventual outcome of masking therapy, however certain measurements may help as a guide to patient management.", "The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Low frequency rTMS applied over the auditory cortex has been proposed as a new and causally oriented treatment approach for pathological conditions with abnormal, increased cortical activity including tinnitus with increased activity in the auditory cortex. However available studies are characterized by a positive reports on the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for treatment of tinnitus, there are few details about the duration of specific treatment effects.\n The design of the study was randomized, prospective, placebo-controlled. Right-handed patients were treated with either real or sham 1 Hz frequency rTMS over a period of two weeks. Fifty-two patients with chronic, treatment resistant tinnitus and stable medication were enrolled in the study after giving written informed consent and forty-two patients completed the study and were included in data analysis.\n The ability to reduce the symptoms of tinnitus appeared in both randomized groups immediately after the 1 Hz rTMS and sham stimulation phase. There was a significant reduction in both groups of the tinnitus total score on the Tinnitus Handicap Inventory (THI) (real rTMS p=0.005; sham rTMS p=0.049) and Tinnitus Questionnaire (TQ) total score (real rTMS p=0.003; sham rTMS p=0.049). On the THI evaluation scale, in the real rTMS a mild worsening was noted during week 6 in comparison with the state attained in week 2. During the subsequent course of the study a significant reduction of the total score persisted in the case of THI (real rTMS week 14 p=0.033 and borderline week 26 p=0.058). The reduction of symptoms as evaluated using the TQ was significant compared to baseline in the real rTMS group at week 2, 6 and 14 (p=0.003; p=0.024; p=0.022). The group treated with sham stimulation reached significant reduction of symptoms only at week 2 (p=0.049). A comparison of the difference in the recorded values of the total score during follow-up in relation to baseline expressed as a percentage demonstrates the difference in the effect of rTMS and sham stimulation as evaluated by both the basic scales. Graphical analysis of mean patterns of treatment response according to stimulation type shows a similarity between treatment response patterns evaluated by reduction of the total scores using THI and TQ.\n The principal finding of this study is that real 1 Hz rTMS treatment was capable of significantly reducing the total baseline score of basic scales that measure tinnitus severity. This result is important as it proves that significant reduction of symptoms can be achieved even in a group of patients with long-term symptoms resistant to pharmacological treatment.", "Tinnitus is a frequent disorder which is very difficult to treat and there is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Targeted modulation of tinnitus-related cortical activity has been proposed as a promising new treatment approach. We aimed to investigate both immediate and long-term effects of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with tinnitus and normal hearing.\n Using a parallel design, 20 patients were randomized to receive either active or placebo stimulation over the left temporoparietal cortex for five consecutive days. Treatment results were assessed by using the Tinnitus Handicap Inventory. Ethyl cysteinate dimmer-single photon emission computed tomography (SPECT) imaging was performed before and 14 days after rTMS.\n After active rTMS there was significant improvement of the tinnitus score as compared to sham rTMS for up to 6 months after stimulation. SPECT measurements demonstrated a reduction of metabolic activity in the inferior left temporal lobe after active rTMS.\n These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least 6 months and significant reduction of neural activity in the inferior temporal cortex, despite the stimulation applied on the superior temporal cortex.", "In 20 patients diagnosed with Menière's disease, transcutaneous nerve stimulation (TNS) and applied relaxation (AR) were used as a treatment aimed at reducing tinnitus and dizziness and increasing hearing ability. The main aim of the study was to examine whether TNS could be regarded as a more beneficial treatment regimen than AR. An experimental between-group cross-over design was used. The results from the experimental phase (group comparisons) showed a significantly increased ability to hear for the TNS group when measured on visual analogue scales. During the same period, the AR-group showed a significant hearing improvement for the ear not primarily affected by Menière's disease as measured with pure tone audiometry. The vestibular tests did not reveal any significant changes either after TNS or AR intervention. Tinnitus matching showed changes of pitch and loudness before and after both TNS and AR intervention. However, no statistically significant changes between treatment regimes were found on these measures. The results from this study did not show TNS to be superior to AR in reducing tinnitus, dizziness or increasing hearing ability.", "Tinnitus is a common symptom, defined as a sound perception in absence of a sound stimulus.\n Evaluate if Trazodone, an antidepressant drug, which modulates serotonin at central neuronal pathways, is effective in controlling tinnitus.\n Prospective, double blind, randomized, placebo-controlled.\n Study performed with patients presenting tinnitus. 85 patients were analyzed between February and June of 2005. 43 received trazodone and 42 placebo, for 60 days. The clinical criteria of analysis were tinnitus intensity, discomfort and life quality impact by tinnitus, using an analogue scale varying between 0 and 10, scored by patients before and after drug or placebo use.\n There was a significant improvement in intensity, discomfort and life quality in both groups after treatment; however, there was no significant difference between the drug and placebo groups. Patients with age equal or over 60 years presented better results after treatment.\n Trazodone was not efficient in controlling tinnitus in the patients evaluated under the doses utilized.", "We compared the effect of different frequencies of repetitive transcranial magnetic stimulation (rTMS) (1 Hz, 10 Hz, 25 Hz and sham (occipital, 1 Hz)), given daily over the left temporoparietal cortex for 2 weeks, on 66 patients with chronic tinnitus randomly divided into four treatment groups. Patients were assessed using the Tinnitus Handicap Inventory, self-ratings of symptoms and audiometric measures of residual inhibition before, immediately after 2 weeks' treatment and monthly thereafter for 4 consecutive months.\n There were no significant differences in basal measures between the four groups of patients. A two-factor ANOVA revealed a significant \"rTMS\" x \"time\" interaction for all measures. This was because real rTMS produced greater improvement than sham. However, there was no significant difference between the responses to different frequencies of rTMS. The response to rTMS depended on the duration of tinnitus: patients who had tinnitus for the longest period of time were the least likely to respond to treatment.\n Daily sessions of rTMS over the temporoparietal cortex may be a useful potential treatment for tinnitus.", "The efficiency of two treatment modalities for subjective/idiopathic tinnitus (SIT): biofeedback (BF) and amitriptyline hydrochloride (AT) was investigated in 225 randomly selected subjects. Findings show that after 10 weeks of treatment in the BF group, 43.5% of the patients reported an improvement of tinnitus during activity. In the AT group, 27.5% of patients reported subjective improvement of tinnitus at rest although only 15.8% of the AT patients reported improvement during activity. Biofeedback during rest had a significantly better effect on tinnitus disturbance than AT. No objective diminishment of tinnitus loudness was found as a result of any of the treatment modalities. We believe that BF can help tinnitus patients especially during periods of rest and we also suggest trying tricyclic antidepressant drugs such as AT for treatment of tinnitus patients, in small doses, however, to minimize the side effects of this drug. Subjective tinnitus (ST) is one of the most common and yet most unclear of otologic symptoms.(1-4) ST can accompany any type of hearing loss including both sensorineural as well as conductive hearing loss, and may originate from any part of the auditory pathway.(1,5) Treatment of ST must be primarily directed to the basic illness diagnosed after a thorough general ear-nose-throat and neurologic evaluation.(6) Severity of ST is evaluated both objectively, by determining the pitch and intensity of the tinnitus,(7) and subjectively as described by the patient. Because of the relatively high incidence of ST and in some patients, the severe personal reaction to it, many different treatments have been suggested, but generally only small to moderate success has been achieved in reducing tinnitus and its consequences, if any at all.(8) In this study we examined the effect of two treatment modalities: amitriptyline hydro-chloride and biofeedback." ]

[ "17094744", "7508066", "6193578", "9403744", "8583588", "10192146", "364393", "1884733", "2183488" ]

[ "Forced versus minimal intravenous hydration in the management of acute renal colic: a randomized trial.", "Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences.", "Acute ureteral colic and fluid intake.", "Protocol-guided diuretic management: comparison of furosemide by continuous infusion and intermittent bolus.", "Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study.", "Concomitant treatment with urodilatin (ularitide) does not improve renal function in patients with acute renal failure after major abdominal surgery--a randomized controlled trial.", "Furosemide in hyaline membrane disease.", "Comparative study of the efficacy of dipyrone, diclofenac sodium and pethidine in acute renal colic. Collaborative Group of the Spanish Society of Clinical Pharmacology.", "Intramuscular diclofenac sodium versus intravenous Baralgin in the treatment of renal colic." ]

[ "The management of acute renal colic is a problem commonly encountered by both urologists and emergency medicine physicians. The classic approach to managing uncomplicated acute renal colic involves hydration, along with imaging and pain control. Previous studies have suggested that hydration has a significant impact on patient comfort, as well as spontaneous stone passage. This study evaluated the effects of maintenance v forced hydration and its effect on the pain experienced from renal colic.\n Forty male and 18 female patients with a mean age of 41 years suspected to have acute renal colic were identified in the emergency department. After screening and informed consent, the patients were enrolled in the study, and 43 patients were eventually available for analysis. Patients received intravenous (IV) analgesia, imaging with a noncontrast CT scan of abdomen and pelvis, and assignment to either forced IV hydration with 2 L of normal saline over 2 hours (N = 20) or minimal IV hydration at 20 mL of normal saline per hour (N = 23). A visual analog pain scale was completed hourly for a total of 4 hours. Demographic information, laboratory and imaging results, narcotic use in morphine equivalents (ME), and pain scores were recorded and compared. Spontaneous stone passage rates were also calculated by careful patient follow-up. Results were considered statistically significant at p < 0.05.\n Stone size was equivalent in the two treatment groups (p > 0.05). There was no difference in the narcotic requirement in ME (p = 0.644) between the two groups. Similarly, there was no difference in hourly pain score or stone-passage rates between the groups (p > 0.05).\n Treatment of uncomplicated renal colic has traditionally included vigorous intravenous hydration, as well as medications for the control of pain and nausea. Our data suggest that maintenance intravenous fluids are as efficacious as forced hydration with regard to patient pain perception and narcotic use. Moreover, it appears the state of hydration has little impact on stone passage.", "We examined the biochemical changes and the efficacy of indapamide in the prevention of calcium stone recurrences. Seventy-five patients with calcium nephrolithiasis and hypercalciuria were randomly assigned to three different therapies: diet and fluid (group A), diet and fluid plus indapamide 2.5 mg/day (group B), and diet and fluid plus indapamide 2.5 mg/day plus allopurinol 300 mg/day (group C). Before treatment and after 6, 12, 24, and 36 months of therapy, we evaluated blood pressure, serum and urine risk parameters (including relative supersaturations of calcium oxalate, calcium phosphate and uric acid), stone rate, and the proportion of calculi-free patients. During the 3 years of treatment, urinary calcium greatly decreased in groups B and C, dropping to 50% of the pretreatment values; urinary oxalate also significantly declined in group B (-24%) and group C (-27%). Relative supersaturations of calcium oxalate and calcium phosphate decreased to the same extent in groups B and C (about one-half of the pretreatment value), and relative supersaturation of uric acid was particularly reduced in group C (-65% of the pretreatment value). The stone rate improved in all three groups (p < 0.005), but using actuarial analysis in the evaluation of calculi-free patients, indapamide, and indapamide plus allopurinol groups were found to have a significantly more favorable effect than diet and fluid treatment (p < 0.02), without any difference between the two drug groups. Because indapamide has fewer side effects than thiazide diuretics, we conclude that indapamide could be an interesting alternative to thiazides in the prevention of calcium stones in hypercalciuric patients.", "In the treatment of acute ureteral colic opinions differ regarding the consequences of fluid intake. This study was undertaken to evaluate a possible relationship between fluid load and the pain. One group of patients received 3 liters of fluid intravenously, while in another group all fluids were withheld. No intergroup differences as regards pain was found after 6 hours of observation.", "To evaluate the safety and relative effectiveness of two diuretic protocols in the intensive care unit (ICU).\n Prospective, randomized comparative study.\n Thirty-three cardiac and medical ICU patients with pulmonary edema or fluid overload for which aggressive diuresis was intended.\n Enrolled patients were randomized to fluid management strategies combining fluid restriction and individually adjusted diuretic therapy by either continuous or bolus infusions of furosemide, titrated to achieve negative hourly fluid balance.\n Cumulative intake minus output (primary endpoint); change in serum creatinine, and length of ICU and hospital stay (secondary endpoints). Diuresis by either protocol was feasible, safe, and effective. The main outcome measures were not significantly different for either group managed with a standardized protocol.\n Protocol-guided diuretic management, with individualized titration of dosage to defined physiologic endpoints can be readily and safely implemented in the ICU. Both continuous and bolus diuretic regimens appear equally effective in achieving negative fluid balance. Larger studies with a randomized control arm are needed before these protocols can be recommended as routine practice.", "We define the role of urine volume as a stone risk factor in idiopathic calcium stone disease and test the actual preventive effectiveness of a high water intake.\n We studied 101 controls and 199 patients from the first idiopathic calcium stone episode. After a baseline study period the stone formers were divided by randomization into 2 groups (1 and 2) and they were followed prospectively for 5 years. Followup in group 1 only involved a high intake of water without any dietetic change, while followup in group 2 did not involve any treatment. Each year clinical, laboratory and radiological evaluation was obtained to determine urinary stone risk profile (including relative supersaturations of calcium oxalate, brushite and uric acid by Equil 2), recurrence rate and mean time to relapse.\n The original urine volume was lower in male and female stone formers compared to controls (men with calcium oxalate stones 1,057 +/- 238 ml./24 hours versus normal men 1,401 +/- 562 ml./24 hours, p < 0.0001 and women calcium oxalate stones 990 +/- 230 ml./24 hours versus normal women 1,239 +/- 440 ml./24 hours, p < 0.001). During followup recurrences were noted within 5 years in 12 of 99 group 1 patients and in 27 of 100 group 2 patients (p = 0.008). The average interval for recurrences was 38.7 +/- 13.2 months in group 1 and 25.1 +/- 16.4 months in group 2 (p = 0.016). The relative supersaturations for calcium oxalate, brushite and uric acid were much greater in baseline urine of the stone patients in both groups compared to controls. During followup, baseline values decreased sharply only in group 1. Finally the baseline urine in patients with recurrences was characterized by a higher calcium excretion compared to urine of the patients without recurrences in both groups.\n We conclude that urine volume is a real stone risk factor in nephrolithiasis and that a large intake of water is the initial therapy for prevention of stone recurrences. In cases of hypercalciuria it is suitable to prescribe adjuvant specific diets or drug therapy.", "Acute renal failure after major abdominal surgery is a severe complication in critically ill patients in intensive care units (ICU). The aim of the study was to investigate the effect of urodilatin on the peak value and course of serum creatinine in patients with acute renal insufficiency after major abdominal surgery and the necessity of apparatus-based renal replacement treatment. Furthermore, the incidence and nature of adverse events under urodilatin was documented. In a prospective randomized double-blind placebo-controlled study, 12 critically ill patients after major abdominal surgery with acute renal failure in an intensive care unit (ICU) received 20 ng/kg b.w./min urodilatin (ularitide, INN) or placebo in addition to the standard diuretic therapy or low-dose dopamine (2.5 micrograms/kg b.w./min) and furosemide (1000 mg/24 hr) for a minimum of 96 hours. All patients received mechanical ventilation. Both groups had similar serum creatinine values on the day before the onset of urodilatin/placebo infusion (2.80 +/- 0.24 mg/dl, 2.93 +/- 0.48 mg/dl). Peak serum creatinine was lower in the urodilatin group (4.65 +/- 0.57 mg/dl) compared to vehicle treatment (5.78 +/- 1.58 mg/dl), although the difference did not reach statistical significance (P = 0.148). The total number of hemodialyses due to oligo-/anuria and/or hyperkalemia was the same in both groups during the study. In 4 patients of the placebo group, diuresis was reduced to anuria, whereas only 1 of the patients treated with urodilatin became anuric. No hemodynamic side effects or adverse events due to urodilatin were observed. This clinical study under double blind conditions revealed that the addition of urodilatin to the standard diuretic therapy of low-dose dopamine and furosemide failed to improve renal function in patients with established acute renal failure and that urodilatin did not eliminate the need for apparatus-based renal replacement treatment.", "In a randomized clinical trial designed to evaluate the effect of diuresis on infants with hyaline membrane disease, seven infants were treated with furosemide (2 mg/kg intravenously) and five received 5% dextrose water in 0.225% sodium chloride (control group). Arterial blood gas analyses performed before and during the six hours after treatment showed no significant difference between control and treated infants. Urine output and urine sodium and calcium loss were significantly increased (P less than .05) in the infants receiving furosemide. The diuresis seemed to have no effect on left atrial size determined echocardiographically, whereas measurements of dynamic skinfold thickness suggested mobilization of subcutaneous water. One infant became seriously dehydrated and hypotensive secondary to a massive diuresis. We concluded that furosemide had a potent diuretic effect in infants with hyaline membrane disease but does not improve cardiorespiratory function acutely. This may be because of failure to mobilize pulmonary interstitial fluid in the time period tested. It may also be possible that the presence of pulmonary interstitial fluid does not play an important role in the impairment of gas exchange in the acute stage of hyaline membrane disease.", "A randomized, double-blind, multicentre clinical trial was designed to compared the analgesic efficacy of i.m. dipyrone 1 and 2 g, i.m. diclofenac sodium and i.m. pethidine in acute renal colic. The study was carried out in 451 patients in 13 Spanish hospitals. Ureteric colic was diagnosed by the clinical features, urinalysis, or when the presence of a ureteric calculus was confirmed. The severity of pain was assessed by the physicians and by patients using visual analogue scales. The main parameter of drug efficacy was the need for rescue treatment-pethidine 100 mg i.m. 30 min after the experimental treatment. Rescue treatment was required in 93 patients: they represented 24.1% of the group given dipyrone 1 g; 22.3% of those on dipyrone 2 g; 16.4% of those given diclofenac sodium; and 19.5% of those on pethidine. The differences between the groups were not significant. In the remaining 358 patients, no difference between treatments was observed. The results suggest that in acute renal colic the use of dipyrone 2 g is unjustified as dipyrone 1 g is equally effective. Diclofenac sodium is a valid alternative, which shows similar analgesic efficacy.", "A comparative, randomized, double-blind study of diclofenac sodium 75 mg im versus Baralgin (a combination drug composed of dipyrone and two spasmolytics) 5 mL iv was performed on 57 patients with renal colic. Both groups were comparable as to age, sex, pain evolution time before treatment, and no treatment for renal colic in the six hours preceding trial drug administration. No significant differences were found between the two groups with respect to the evolution of pain after the first dose or in the frequency of administration of a second dose. Tolerability was good in both groups, but sweating and pain throughout the vein were observed in one patient in the Baralgin group. We concluded that diclofenac sodium constitutes an excellent alternative to pyrazolone analgesics, with the advantages of being monotherapy and having good tolerability, when used as intramuscular injection in ambulatory patients." ]

[ "11431176", "17591533", "8052432", "12761258", "11855793", "8167383", "9576406", "9417158", "12692572" ]

[ "Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy.", "ACE inhibitors and persistent left ventricular hypertrophy after renal transplantation: a randomized clinical trial.", "ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study.", "Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial.", "Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study.", "ACE inhibitor mediated reductions in renal size and microalbuminuria in normotensive, diabetic subjects.", "A randomized trial of captopril for microalbuminuria in normotensive adults with sickle cell anemia.", "alpha1-Proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity: a randomized, controlled trial.", "Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease." ]

[ "Angiotensin-converting enzyme (ACE) inhibitors and AT1-receptor antagonists (ARAs) are widely administered to reduce urinary protein loss and slow the progression of proteinuric nephropathy to end-stage renal failure. Our group recently observed that the combination of ACE inhibitors and ARAs may have an additive antiproteinuric effect, which may occur because ACE inhibitors do not completely reduce angiotensin II (Ang II) production. Ang II is also produced by chymase. Thus, combination therapy better antagonizes the effects of Ang II. The purpose of this study is to ascertain whether the additive antiproteinuric effect of ACE inhibitors plus ARAs is dose dependent and related to the drug-induced reduction in systemic blood pressure. Therefore, enalapril (E; 10 mg/d) and losartan (LOS; 50 mg/d) were randomly administered alone and then in association; initial dosages were doubled when drugs were administered alone and in association. To determine the influence of the drug-dependent effect on reducing blood pressure and the reduction in urinary proteinuria, both ambulatory and office blood pressures were recorded. E and LOS administered alone reduced proteinuria by the same extent; no further reduction was observed when E and LOS alone were administered at a doubled dose. When E and LOS were coadministered, proteinuria decreased by a greater extent compared with E and LOS alone; an additional reduction in proteinuria was observed when combined therapy doses were doubled. The reduction in proteinuria was not correlated with clinical through blood pressure; however, reductions in diastolic and mean ambulatory blood pressures significantly correlated with the decrease in proteinuria, as well as with creatinine clearance. In conclusion, this study shows that combination therapy with E and LOS has an additive dose-dependent antiproteinuric effect that is likely induced by the drug-related reduction in systemic blood pressure. In normotensive proteinuric patients, it is likely that even a small reduction in systemic blood pressure may affect intraglomerular hemodynamics by a great extent because efferent arteriole regulation is hampered more completely by the coadministration of ACE inhibitors and ARAs.", "Interventional studies of left ventricular hypertrophy (LVH) in renal transplant recipients are scarce and to date evaluated only patients immediately after renal transplantation.\n Randomized controlled trial that assessed the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in regressing persistent LVH after successful transplantation.\n 70 renal transplant recipients (47 men; age, 30 to 68 years) without diabetes previously randomly assigned to either cyclosporine or tacrolimus therapy, with LVH persisting 3 to 6 months after transplantation.\n Subjects were randomly assigned to either lisinopril (ACE-inhibitor group; 36 patients) or no therapy (control group; 34 subjects).\n Main outcome was change in left ventricular mass index (LVMi) at month 18.\n A consistent decrease in both systolic (SBP) and diastolic blood pressure (DBP) was observed in both groups (between-group differences, -1.7 +/- 3.3 mm Hg; 95% confidence interval [CI], -4.8 to 8.2; P = 0.6 for SBP; 0.3 +/- 2.2 mm Hg; 95% CI, -4.8 to 4.1; P = 0.9 for DBP), whereas LVMi regressed more in the ACE-inhibitor group (between-group difference, 10.1 +/- 16.3 g/m(2.7); 95% CI, 4.2 to 16.1; P < 0.01). A significant interaction of ACE inhibitors with cyclosporine in affecting LVMi change was shown by means of post hoc multiple regression analysis (P < 0.01; differences between cyclosporine and tacrolimus group, 13.3 +/- 3.9 g/m(2.7); 95% CI, 5.3 to 21.2; P < 0.01 in the ACE-inhibitor group; 3.7 +/- 4.2 g/m(2.7); 95% CI, -4.7 to 12.2; P = 0.4 in the control group).\n Single-center study with small sample size. Interaction of ACE inhibitors with cyclosporine treatment emerged from post hoc analysis.\n A prolonged course of ACE-inhibitor therapy is effective in regressing the persistent LVH of renal transplant recipients by mechanisms independent of effects on BP. This regression seems to be at least in part the effect of an interaction between ACE inhibitors and cyclosporine.", "A multicentre, randomized, placebo-controlled study was performed in 39 adult patients with biopsy-proven IgA nephropathy with the aim of comparing the effects of the ACE inhibitor fosinopril and placebo on proteinuria. All patients had normal blood pressure and normal renal function. Proteinuria ranged from 1.0 to 2.5 g/24 h. After a 3-month run-in period, fosinopril and placebo were randomly administered in two 4-month sequences separated from cross-over treatment by a 1-month interval. The mean values of creatinine clearance did not change during either the placebo or the treatment sequences. The mean values of mean arterial pressure (MAP) were significantly lower during the fosinopril sequence (90.4 +/- 9.0 mmHg) than in basal conditions (92.8 +/- 9.1 mmHg) (P = 0.034). The mean basal values of proteinuria were 1.74 +/- 0.84 g/24 h. They were unchanged during the placebo sequence (1.79 +/- 1.20) and fell to 1.37 +/- 0.98 g/24 h after 4 months of fosinopril treatment. Using a multivariate statistical analysis, the treatment effect by time on proteinuria was significantly evident only in the fosinopril sequence (Wilks test, P = 0.033). Changes in protein excretion were not correlated with changes in MAP, baseline plasma renin activity, and urinary sodium excretion. This controlled study shows that fosinopril can significantly reduce proteinuria even in normotensive patients with IgA nephropathy. Obviously, the results of treatment with ACE inhibitors on long-term renal prognosis remain to be elucidated.", "Some retrospective studies have suggested a beneficial influence of angiotensin-converting enzyme (ACE) inhibitors on the progression of IgA nephropathy (IgAN), but prospective and controlled studies demonstrating this effect are lacking. Forty-four patients with biopsy-proven IgAN, proteinuria > or = 0.5 g/d, and serum creatinine (SCr) < or = 1.5 mg/dl were randomly assigned either to receive enalapril (n = 23) or to a control group (n = 21) in whom BP was controlled with antihypertensives other than ACE inhibitors. Primary outcome was renal survival estimated by a 50% increase in baseline SCr. Secondary outcomes were the presence of a SCr > 1.5 mg/dl at the last visit and the evolution of proteinuria. Baseline clinical findings were similar at baseline between enalapril-treated and control group, and there were no differences in BP control during follow-up. Mean follow-up was 78 +/- 37 mo in the enalapril group and 74 +/- 36 mo in the control group. Three patients (13%) in the enalapril group and 12 (57%) in the control group reached the primary end point (P < 0.05). Kaplan-Meier renal survival was significantly better in enalapril group than in control group: 100% versus 70% after 4 yr and 92% versus 55% after 7 yr (P < 0.05). Three patients in the enalapril group (13%) and 11 (52%) in the control group showed SCr > 1.5 mg/dl at the last visit (P < 0.05). Proteinuria significantly decreased in the enalapril group, whereas it tended to increase in the control group (P < 0.001 between groups). In conclusion, ACE inhibitors significantly improve renal survival in proteinuric IgAN with normal or moderately reduced renal function.", "We compared the efficacy of treatment protocols with an angiotensin converting enzyme (ACE) inhibitor alone (enalapril, 5 mg) or angiotensin II (ATII) receptor blocker (losartan, 50 mg) or both enalapril plus losartan in patients with microalbuminuria in a prospective, randomized clinical trial. Normotensive type 2 diabetic patients with microalbuminuria documented by at least 3 consecutive urinary albumin excretion analyses were recruited for the study. Patients were grouped randomly into one of the protocols which consisted of treatment with 5 mg enalapril daily (group 1; n=12), 50 mg losartan daily (group 2; n=12) or both drugs (group 3; n=10). They were reevaluated with regard to HbA1c levels, lipid profiles, blood pressure and urinary albumin excretion rates (UAER) at 3-month intervals for 12 months. Mean age, duration of diabetes, body mass index, plasma lipid profiles and blood pressure levels were similar at the initial visit. In group 1, UAER returned to normal levels in 10 patients. Normalization of UAER occurred in 8 and 7 patients in groups 2 and 3, respectively. Percentage of reduction in UAERs at the end of 12 months were 58%, 59% and 60% (p=0.0001; p=0.0002; p=0.0003, respectively). The amount of reduction in UAER did not differ significantly among the three groups (p=0.346). ACE inhibitors and angiotensin II receptor blockers have similar efficacy in treating diabetic microalbuminuria, and the combination of the two drugs does not add any further benefit.", "Recent studies utilizing converting enzyme inhibitors (CEI) in diabetic rats document reductions in both renal hypertrophy and albuminuria. Four separate clinical studies in normotensive patients with diabetes demonstrate reduction of microalbuminuria with CEIs independent of blood pressure reduction. The present pilot study examines the results of reducing an elevated glomerular filtration rate on changes in renal size and microalbuminuria in normotensive, hyperfiltering insulin-dependent diabetic (IDDM) patients. Fifteen IDDM patients were randomized to either placebo or the CEI, lisinopril. Dosage of lisinopril was titrated over 3 months to reduce glomerular filtration rate (GFR) to < or = 2.33 mL/sec. Evaluation at 18 months demonstrated the lisinopril group had a marked reduction in renal size (16.9 +/- 1.1, baseline versus 12.8 +/- 0.9 cm, 18 months; p < 0.05) and microalbuminuria (92 +/- 11 micrograms/min, baseline versus 23 +/- 26 micrograms/min, 18 months; p < 0.05). No change in renal size was noted in the placebo group (15.4 +/- 0.8, baseline versus 14.9 +/- 0.7 cm, 18 months; NS) and albuminuria increased (118 +/- 15 micrograms/min, baseline versus 293 +/- 32 micrograms/min, 18 months; p < 0.05). Mean arterial pressure at 18 months was significantly lower in the lisinopril group compared to placebo (102 +/- 4, placebo versus 87 +/- 6 mm Hg, CEI, p < 0.05). This study supports previous animal studies that document reductions in both microalbuminuria and renal size by a CEI. The overall impact of these findings on preservation of renal function cannot be assessed, however, in this short-term study.", "Nephropathy is a common complication of sickle cell anemia and is often preceded by proteinurea. Our aim was to evaluate the effect of angiotensin-converting enzyme inhibition on microalbuminuria in sickle cell patients.\n We performed a randomized, double-blind, placebo-controlled trial in 22 normotensive patients with sickle cell anemia and persistent microalbuminuria. Patients received captopril (25 mg/day) or placebo and were followed up for 6 months. Albuminuria, blood pressure, and serum creatinine and hemoglobin concentrations were measured at baseline and at 1, 3, and 6 months. The primary outcome variable was the 6-month change in albuminuria between the two groups.\n Baseline albuminuria was 121 (SD 66) mg per 24 hours in the captopril group and 107 (SD 86) mg per 24 hours in the placebo group. Microalbuminuria decreased from baseline in the captopril group but increased in the placebo group. The mean absolute change and the mean percentage change in microalbuminuria were significantly different between the two groups at 6 months (absolute change -45 mg per 24 hours in the captopril group versus +18 mg per 24 hours in the placebo group, P <0.01; and percentage change -37% in the captopril group versus +17% in the placebo group, P <0.01). The 95% confidence intervals (CI) for the difference in albuminuria between the two groups were 63 (CI 40 to 86) mg per 24 hours for the mean absolute change and 54% (CI 22% to 85%) for the mean percentage change. Blood pressure decreased slightly from baseline in captopril-treated patients and did not change in the placebo group. The change was significantly different between the two groups only for diastolic blood pressure at 6 months (P <0.01).\n Captopril reduces albuminuria and slightly decreases blood pressure in patients with sickle cell anemia. More studies are required to demonstrate the sustained benefit on protein excretion.", "An imbalance between increased neutrophil elastase and a decreased antiprotease shield has been suggested as a factor contributing to the development of chronic lung disease (CLD). We hypothesized that administration of alpha1-proteinase inhibitor (A1PI), also known as alpha1-antitrypsin, to premature neonates would prevent CLD.\n A randomized, placebo-controlled, prospective study of A1PI supplementation was performed. Neonates <24 hours of age with birth weights 600-1000 g on respiratory support, and 1001-1250 g with respiratory distress syndrome (RDS) were eligible. Intravenous A1PI (60 mg/kg) or placebo was infused on days 0, 4, 7, and 14. Primary outcome was CLD in survivors, defined as the need for supplemental oxygen on day 28.\n A total of 106 patients were recruited. There were no significant differences between groups in birth weight or incidence of RDS. The incidence of CLD in survivors was lower in the treated group, but the difference did not reach statistical significance (relative risk [RR], 0.79; confidence interval [CI], 0.60-1.02). This beneficial trend persisted at 36 weeks corrected gestational age (RR, 0.48; CI, 0.23-1.00). The incidence of pulmonary hemorrhage was lower in the treated group (RR, 0.22; CI, 0.05-0.98). Other complications were not significantly different between groups.\n In this, the first trial of a protease inhibitor for the prevention of CLD in premature infants, the infusions were well-tolerated. A1PI therapy may impede the development of CLD and appears to reduce the incidence of pulmonary hemorrhage in some neonates born prematurely.", "Although the angiotensin receptor antagonist (ARB) shares the angiotensin-II-blocking activity with the angiotensin-converting enzyme inhibitor (ACE-I), pharmacological mechanisms of action of these agents differ. We evaluated the temporal profiles of action of ACE-I and ARB on urinary protein excretion and nitrate/nitrate (NO(x)) excretion in hypertensive (140 and/or 90 mmHg) patients with chronic renal disease (serum creatinine < 265 (range, 44-265) micromol/l or creatinine clearance > 30 (range, 30-121) ml/min). Patients with mild (<1 g/day; range, 0.4-1.0) and moderate proteinuria (>1 g/day; range, 1.1-6.9) were randomly assigned to ACE-I- and ARB-treated groups, and were treated with ACE-I (trandolapril or perindopril) or ARB(losartan or candesartan) for 48 weeks. In all groups, treatment with ACE-I or ARB decreased blood pressure to the same level, but had no effect on creatinine clearance. In patients with mild proteinuria, neither ACE-I nor ARB altered urinary protein excretion. In patients with moderate proteinuria, ACE-I caused 44 +/- 6% reduction in proteinuria (from 2.7 +/- 0.5 to 1.5 +/- 0.4 g/day, n = 14) at 12 weeks, and this beneficial effect persisted throughout the protocol (48 weeks, 1.2 +/- 0.2 g/day). In contrast, ARB did not produce a significant decrease in proteinuria at 12 weeks (23 +/- 8%, n = 13), but a 41 +/- 6% reduction in proteinuria was observed at 48 weeks. Similarly, although early (12 weeks) increases in urinary NO(x) excretion were observed with ACE-I (from 257 +/- 70 to 1111 +/- 160 micromol/day) and ARB (from 280 +/- 82 to 723 +/- 86 micromol/day), the ARB-induced increase in NO(x) excretion was smaller than that by ACE-I (P < 0.05). In conclusion, although both ACE-I and ARB reduce blood pressure similarly, the effect of these agents on proteinuria differs in chronic renal disease with moderate proteinuria. Relatively early onset of the proteinuria-reducing effect was observed with ACE-I, which paralleled the increase in urinary NO(x) excretion. Conversely, ARB decreased proteinuria and increased urinary NO(x) excretion gradually. These time course-dependent changes in proteinuria and urinary NO(x) may reflect the pharmacological property of ACE-I and ARB, with regard to the action on bradykinin." ]

[ "18237352", "18755784", "10117742", "19775439", "9097333", "7974314", "11716652", "12495948", "11902848" ]

[ "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "Promotion of health in older people: a randomised controlled trial of health risk appraisal in British general practice.", "The impact of increasing intensity of health promotion intervention on risk reduction.", "A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies.", "Psychophysiological concomitants of organizational change in health care personnel: effects of a controlled intervention study.", "Prospective controlled evaluation of the effect of a community based asthma education centre in a multiracial working class neighbourhood.", "Evaluation of a multicomponent workplace health promotion program conducted in Japan for improving employees' cardiovascular disease risk factors.", "Randomised controlled trial of site specific advice on school travel patterns.", "Effects of a tailored health promotion program for female blue-collar workers: health works for women." ]

[ "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation.", "there is inadequate evidence to support currently formulated NHS strategies to achieve health promotion and preventative care in older people through broad-based screening and assessment in primary care. The most extensively evaluated delivery instrument for this purpose is Health Risk Appraisal (HRA). This article describes a trial using HRA to evaluate the effect on health behaviour and preventative-care uptake in older people in NHS primary care.\n a randomised controlled trial was undertaken in three London primary care group practices. Functionally independent community-dwelling patients older than 65 years (n = 2,503) received a self-administered Health Risk Appraisal for Older Persons (HRA-O) questionnaire leading to computer-generated individualised written feedback to participants and general practitioners (GPs), integrated into practice information-technology (IT) systems. All primary care staff received training in preventative health in older people. The main outcome measures were self-reported health behaviour and preventative care uptake at 1-year follow-up.\n of 2,503 individuals randomised, 2,006 respondents (80.1%) (intervention, n = 940, control n = 1,066) were available for analysis. Intervention group respondents reported slightly higher pneumococcal vaccination uptake and equivocal improvement in physical activity levels compared with controls. No significant differences were observed for any other categories of health behaviour or preventative care measures at 1-year follow-up.\n HRA-O implemented in this way resulted in minimal improvement of health behaviour or uptake of preventative care measures in older people. Supplementary reinforcement involving contact by health professionals with patients over and above routine clinical encounters may be a prerequisite to the effectiveness of IT-based delivery systems for health promotion in older people.", "The HealthWise Stepped Intervention Study (1988-1990) at Pacific Gas and Electric was conducted to evaluate how a health promotion program affects behavior change and whether increasing levels of preventive interventions improve health status. The basic intervention components consisted of health risk assessment and health newsletter (Levels 1, 2, 3, and 4). Additional interventions were health resource center and self-care books (Levels 2, 3, and 4), behavioral change workshops and Division Healthwise team (Levels 3 and 4), and case management and environmental policy (Level 4). The study employed a quasi-experimental design with nonequivalent control groups. The overall risk status has significantly improved at all four intervention levels. The comparison across the four intervention levels found that Level 4, combining environmental policy with \"high risk\" targeting, showed the most impressive performance. Participants in Level 4 consistently showed significantly greater improvement in life-style factors, and their overall risk status also showed the greatest improvement.", "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 possible psychophysiological changes in personnel being exposed to organizational change and to assess the effects of a structured empowerment programme.\n A randomized, prospective, controlled, and non-blinded intervention was carried out in two wards within a geriatric hospital. The I-ward (intervention) was offered a structured intervention programme with a trained, registered psychologist during 20 weekly 1-hour sessions before and after the organizational change. The C-ward (control) was passively attended by the same psychologist during equal time conditions. Blood pressure as well as pulse rate were taken and blood samples were drawn from all participants before (0 weeks), immediately after the intervention (20 weeks) and after another 10 weeks' follow-up (30 weeks).\n There was a significant time x group interaction with increasing prolactin levels on the C-ward as compared to decreasing levels on the I-ward during the intervention.\n Our study results suggest a picture of differentiated changes in stress hormone levels. The I-ward exhibited less psychoendocrine stress compared to the C-ward, probably due to the intervention and the possibility for personnel to influence the programme. We suggest that psychosocial empowerment programmes are beneficial when organizational changes are enacted in health care settings.", "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).", "The long-term effectiveness of multicomponent worksite health promotion programs targeting cardiovascular disease risk factors remains unclear in Japan. This study was conducted to evaluate the effectiveness of such a health promotion program consisting of a main program provided over 4 days and a follow-up program provided over 1 year.\n The subjects of this randomized controlled trial were male employees working for a building maintenance company in Japan. The intervention group (n = 152) and the control group (n = 150) consisted of employees having abnormal findings in at least one of the following items at baseline health examination: body mass index (BMI), systolic (SBP) or diastolic blood pressure, total cholesterol, HDL cholesterol, triglycerides, and fasting blood glucose. Evaluation was conducted at 18 months after the main program.\n BMI, SBP, total cholesterol, and triglycerides improved significantly in the intervention group compared with the control group (P < 0.05). When comparisons were limited to those who showed abnormality at baseline, BMI, total cholesterol, and triglycerides improved significantly in the intervention group (P < 0.05).\n The multicomponent health promotion program provided to employees was shown to be effective in improving obesity, high blood pressure, and hyperlipidemia when evaluated 18 months after the main intervention program.\n Copyright 2001 American Health Foundation and Elsevier Science.", "To evaluate the effect of site specific advice from a school travel coordinator on school travel patterns.\n Cluster randomised controlled trial of children attending 21 primary schools in the London boroughs of Camden and Islington. A post-intervention survey measured the proportion of children walking, cycling, or using public transport for travel to school, and the proportion of parents/carers very or quite worried about traffic and abduction. The proportion of schools that developed and implemented travel plans was assessed.\n One year post-intervention, nine of 11 intervention schools and none of 10 control schools had travel plans. Proportions of children walking, cycling, or using public transport on the school journey were similar in intervention and control schools. The proportion of parents who were very or quite worried about traffic danger was similar in the intervention (85%) and control groups (87%). However, after adjusting for baseline and other potential confounding factors we could not exclude the possibility of a modest reduction in parental concern about traffic danger as a result of the intervention.\n Having a school travel coordinator increased the production of school travel plans but there was no evidence that this changed travel patterns or reduced parental fears. Given the uncertainty about effectiveness, the policy of providing school travel coordinators should only be implemented within the context of a randomised controlled trial.", "This study assessed the effects of the Health Works for Women (HWW) intervention on improving multiple behaviors including nutrition and physical activity among rural female blue-collar employees in North Carolina.\n Nine small to mid-size workplaces were randomly assigned to either intervention or delayed intervention conditions. After a baseline survey, an intervention consisting of two computer-tailored magazines and a natural helpers program was conducted over 18 months. Delayed worksites received one tailored magazine. Approximately 77 and 76% of baseline respondents completed follow-up surveys at 6 and 18 months, respectively, and 538 women (63%) completed all three surveys.\n At the 18-month follow-up, the intervention group had increased fruit and vegetable consumption by 0.7 daily servings compared to no change in the delayed group (P < 0.05). Significant differences in fat intake were observed at 6 months (P < 0.05) but not at 18 months. The intervention group also demonstrated improvements in strengthening and flexibility exercise compared to the delayed group. The rates of smoking cessation and cancer screening did not differ between study groups.\n The HWW project was a successful model for achieving certain health behavior changes among blue-collar women.\n (C)2002 American Health Foundation and Elsevier Science (USA)." ]

[ "16500364", "16543255", "18321486", "19396538", "12070543", "11804430", "17239866", "8299789", "18505764" ]

[ "Addition of human chorionic gonadotropin to clomiphene citrate ovulation induction therapy does not improve pregnancy outcomes and luteal function.", "Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study.", "Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: a randomized controlled trial.", "Evaluating the equivalence of clomiphene citrate with and without metformin in ovulation induction in PCOS patients.", "The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome.", "Improved responsiveness of PCOS patients to clomiphene after CYP17a inhibitor.", "hCG administration offers no outcome benefit over spontaneous ovulation in anovulatory women treated with clomiphene citrate.", "Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles.", "Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome." ]

[ "In a randomized prospective study, 125 women with World Health Organization class II anovulation received 50 mg of clomiphene citrate alone (group A, n = 65) or 50 mg of clomiphene citrate plus hCG (group B, n = 60) in a total of 125 cycles during natural intercourse-advised cycles. There were no statistically significant differences between groups regarding pregnancy outcomes and midluteal P levels, but luteal phase length was longer in group A.", "The aim of this work was to evaluate the efficacy of adding dexamethazone (DEX) (high dose, short course) to clomiphene citrate (CC) in CC-resistant polycystic ovary syndrome (PCOS) with normal dehydroepiandrosterone sulphate (DHEAS) in induction of ovulation.\n Eighty infertile women with CC-resistant PCOS were randomly assigned into two groups. Group I: Clomiphene citrate 100 mg/day was given from day 3 to day 7 of the cycle and DEX 2 mg/day from day 3 to day 12 of the cycle. Group II: Same protocol of CC combined with placebo (folic acid tablets) was given from day 3 to day 12 of the cycle. The main outcome was ovulation. Secondary measures included number of follicles >18 mm endometrial thickness and pregnancy rate. Ovarian follicular response was monitored by transvaginal ultrasound. HCG 10,000 U was given when at least one follicle measured 18 mm, and timed intercourse was advised.\n There were no statistically significant differences between groups as regards age, duration of infertility, BMI, waist-hip ratio (WHR), menstrual pattern, hirsutism, serum DHEAS or day of HCG administration. The mean number of follicles>18 mm at the time of HCG administration and the mean endometrial thickness were significantly higher in the DEX group than in the placebo group (P<0.05). Similarly, there were significantly higher rates of ovulation (75 versus 15%) (P<0.001) and pregnancy (40 versus 5%) (P<0.05) in the DEX group. Dexamethazone was very well tolerated as no patients complained of any side effect. There was a significant difference between the responders and non-responders in the presence of oligomenorrhea, amenorrhea or hirsutism.\n Induction of ovulation by adding DEX (high dose, short course) to CC in CC-resistant PCOS with normal DHEAS is associated with no adverse anti-estrogenic effect on the endometrium and higher ovulation and pregnancy rates in a significant number of patients. Induction with DEX appears to be independent on age, period of infertility, BMI or WHR.", "To determine the first-line medication to be used in anovulatory patients with polycystic ovary syndrome (PCOS) for ovulation induction and pregnancy achievement.\n Randomized controlled trial.\n Infertility unit of a public hospital.\n One hundred fifteen newly diagnosed patients with PCOS based on ESHRE/ASRM criteria.\n These patients were assigned to three groups: group 1 (38 patients) received 500 mg of metformin three times a day; group 2 (39 patients) received clomiphene citrate (CC) at an incremental dose; group 3 (38 patients) received both medications.\n Rates of ovulation, pregnancy (PR), and live birth.\n The ovulation rate was 23.7% in the metformin group, 59% in the CC group, and 68.4% in the combination treatment group. This was translated into a similar PR and live birth rate, which were higher in the CC and combination groups compared to the metformin group (PR: 7.9%, 15.4%, and 21.1%; live birth rate: 7.9%, 15.4%, and 18.4% in metformin, CC, and combination treatment groups, respectively), although statistically the differences were not significant. There were no multiple pregnancies and the rate of spontaneous first trimester loss was similar to the general population.\n Clomiphene citrate should be the first-line treatment for ovulation induction in anovulatory patients with PCOS.", "To evaluate the benefit of Metformin added to Clomiphene Citrate in a primary ovulation induction protocol in PCOS patients.\n Prospective randomised controlled study.\n Tygerberg Academic Hospital, Stellenbosch University and the Institute of Reproductive Medicine at Vincent Pallotti Hospital, Cape Town.\n 107 patients presenting with PCOS.\n Group A was pre-treated with metformin 850 mg twice a day for at least 6 weeks before clomiphene was added and the metformin was used throughout the study period. Group B received clomiphene without pre-treatment with metformin. In both groups clomiphene was given at a starting dose of 50 mg day 4-8 and increase with increments of 50 mg to a maximum of 150 mg if no response was achieved.\n The ovulation rate achieved in women in the M+C/C arm was 34/52 (65.4%) compared to 36/55 (65.5%) in the C/C arm. The treatment effect ((M+C/C) - C/C) is 0% with 95% confidence interval of -18.1% to 18%. The per protocol ovulation results were 34/42 (81%) in the M+C/C arm compared to 36/48 (75%) in the C/C arm. The ovulation rate difference was 6% with 95% confidence interval -11% to 22%. In a comparison of successful ovulating versus non-ovulating women from the trial the following were significant baseline determinants: lower median weight in the ovulating group (77 kg versus 86 kg, p = .021), lower median bmi (29.0 versus 32.9, p = .009), lower median DHEAS at baseline (4.6 compared to 7.0, p = .049), lower median 17OH-progesterone (2.2 versus 4.6, p = .027) and higher baseline median SHBG ( 37.8 compared to 28.5, p = .036).\n Although identical ovulation rates were observed in both arms equivalence could not be concluded with respect to the specified criteria.", "To study the effect of metformin in combination with clomiphene citrate, as compared with placebo plus clomiphene citrate, on the ovulation and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.\n This study was carried out at King Hussein Medical Center, Amman, Jordan, during the period January 2001 through to July 2001. Twenty-eight clomiphene citrate-resistant polycystic ovary syndrome women were evaluated prospectively for 6 treatment cycles by receiving metformin, 850mg twice daily throughout the cycle along with 50 mg clomiphene citrate, starting on day 5-9 of the same cycle (N=16), or by taking placebo with clomiphene citrate (N=12). During cycles 2-6, clomiphene citrate was added with increments of 50mg (up to 200 mg/day) for both groups. Progesterone level on day 21 and 28 >5ng/dl was indicative of ovulation.\n A statistically significant increase in the rates of ovulation (68.6% versus 25%, p<0.05) and pregnancy (56.3% versus 16.6%, p<0.05) were observed in the metformin-clomiphene citrate group as compared with the placebo-clomiphene citrate controls. Insignificant increase in the rate of ovarian hyperstimulation was noted in the placebo-clomiphene citrate group.\n Metformin-clomiphene citrate regimen in resistant-clomiphene citrate polycystic ovary syndrome women significantly increases the ovulation and pregnancy rates, and decreases the occurrence of ovarian hyperstimulation syndrome.", "To study the effect of CYP17a inhibitor, \"ketoconazole,\" on clomiphene responsiveness in PCOS patients.\n Prospective analysis was employed with the setup at Alexandria IVF/ICSI center. Ninety-seven insulin-resistant PCOS patients undergoing ovulation induction using clomiphene citrate were randomly divided, by random number table, into two groups. The first group (n = 49) received ketoconazole (400 mg daily) till correction of metabolic syndrome followed by clomiphene (100 mg/day); the second group (n = 48) receiving clomiphene without ketoconazole pretreatment. Main outcome measures were incidence of clomiphene resistance, monofollicular response, fasting insulin/glucose ratio, serum testosterone, and pregnancy rates.\n The ketoconazole group showed significantly (p < 0.05) higher incidence of monofollicular response (38%), higher pregnancy rates, and significantly less marked antiestrogenic manifestations than did the control group. They also had significantly lower incidence of clomiphene resistance (11.6%), lower serum testosterone levels, less hyperinsulinaemia, than did the control group.\n Ketoconazole improved clomiphene responsivenss in PCOS patients and attenuated its untoward biological effects.", "This randomized controlled trial compared spontaneous ovulation versus hCG-triggered ovulation in anovulatory women treated with clomiphene citrate. No statistically significant differences were observed between the two groups in terms of ovulation and pregnancy rates.", "To test the hypothesis that in couples undergoing IUI, actively managed cycles using clomiphene citrate (CC) stimulation, ultrasound monitoring, and hCG timing will result in increased pregnancy rate (PR) per cycle compared with unstimulated urinary LH-timed cycles.\n Fifty-six couples with unexplained infertility (n = 26) or male factor infertility (n = 30) participated in the study.\n Tertiary academic medical center.\n Prospective, randomized, crossover. Couples were randomized initially to one of the two study groups (treatment A: LH-timed IUI; treatment B: CC-stimulated, hCG-timed IUI). If no pregnancy occurred, each couple alternated between the two regimens during subsequent cycles, up to a total of four cycles.\n Twenty-nine couples completed the study and the analysis of 95 cycles revealed that among the male factor infertility group, one pregnancy occurred during the 26 cycles of each treatment group (PR per cycle of 3.9% for both treatment groups). In contrast, among the unexplained infertility group, there was a marked difference in the effect of treatments. During treatment A only one pregnancy occurred in 20 cycles (PR of 5% per cycle) whereas during treatment B, six pregnancies occurred in 23 cycles (PR of 26.1% per cycle).\n If IUI is chosen as the treatment modality in unexplained infertility, the addition of active ovulation management that includes CC stimulation, ultrasound monitoring of folliculogenesis, and hCG timing of ovulation increases the PR per cycle. In couples with male infertility, PR per cycle is low and is apparently not affected by the addition of active ovulation management.", "When used for ovulation induction, higher doses of clomiphene may lead to antiestrogenic side effects that reduce fecundity. It has been suggested that metformin in combination with clomiphene can restore ovulation to some clomiphene-resistant anovulators with polycystic ovary syndrome (PCOS).\n Our objective was to determine if cotreatment with extended-release metformin (metformin XR) can lower the threshold dose of clomiphene needed to induce ovulation in women with PCOS.\n A secondary analysis of data from the National Institute of Child Health and Human Development Cooperative Multicenter Reproductive Medicine Network prospective, double-blind, placebo-controlled multicenter clinical trial, Pregnancy in Polycystic Ovary Syndrome, was performed.\n Study volunteers at multiple academic medical centers were included.\n Women with PCOS and elevated serum testosterone who were randomized to clomiphene alone or with metformin (n = 209 in each group) were included in the study.\n Clomiphene citrate, 50 mg daily for 5 d, was increased to 100 and 150 mg in subsequent cycles if ovulation was not achieved; half also received metformin XR, 1000 mg twice daily. Treatment was for up to 30 wk or six cycles, or until first pregnancy.\n Ovulation was confirmed by a serum progesterone more than or equal to 5 ng/ml, drawn prospectively every 1-2 wk.\n The overall prevalence of at least one ovulation after clomiphene was 75 and 83% (P = 0.04) for the clomiphene-only and clomiphene plus metformin groups, respectively. Using available data from 314 ovulators, the frequency distribution of the lowest clomiphene dose (50, 100, or 150 mg daily) resulting in ovulation was indistinguishable between the two treatment groups.\n Metformin XR does not reduce the lowest dose of clomiphene that induces ovulation in women with PCOS." ]

[ "12893670", "16585434", "17194269", "16754835", "12700715", "16449469", "16818861", "3046553", "17526456" ]

[ "Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination.", "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 study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.", "Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.", "Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine.", "Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.", "Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison.", "Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine.", "Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study." ]

[ "Although there is a consensus that clozapine is more effective than conventional antipsychotic drugs for treatment-resistant schizophrenia, there is great heterogeneity among results of relevant trials.\n To re-evaluate the evidence comparing clozapine with conventional antipsychotics and to investigate sources of heterogeneity.\n Individual studies were inspected with assessment of clinical relevance of results. Meta-regression analysis was performed to investigate sources of heterogeneity.\n Ten trials were examined. Recent large-scale studies have not found a substantial advantage for clozapine, especially in terms of a clinically relevant effect. Meta-regression showed that shorter study duration, financial support from a drug company and higher baseline symptom score consistently predicted greater advantage of clozapine.\n It may be inappropriate to combine studies in meta-analysis, given the degree of heterogeneity between their findings. The benefits of clozapine compared with conventional treatment may not be substantial.", "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.", "Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy.\n This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003.\n Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group.\n Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.", "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.", "The purported advantages of second-generation or \"atypical\" antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia. This flexible-dose study examined efficacy and safety in a randomized, double-blind, 52-week trial, comparing chlorpromazine (CPZ) and clozapine (CLZ) in treatment naive patients experiencing their first episode of schizophrenia. In all, 160 inpatients with first-episode schizophrenia or schizophreniform disorder were randomized to CPZ or CLZ and followed them for 52 weeks or until dropout. The primary efficacy measure was time to first remission and proportion of time remaining in remission. The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects. Of these first-episode patients, 80% achieved remission within 1 year (79% CPZ, 81% CLZ). The Kaplan-Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ (chi(2)(1)=5.56, p=0.02). Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group. At 12 weeks, CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any. These symptom differences remained significant when controlling for EPS differences. By 52 weeks many of the symptom differences between groups were no longer significantly different. Generally, CLZ produced fewer side effects than CPZ, particularly extrapyramidal side effects. There was no significant difference between treatments in weight change or glucose metabolism. For each prior year of untreated psychosis, there was a 15% decrease in the odds of achieving remission (OR=0.85; CI 0.75-0.95). A high proportion of first-episode patients remitted within 1 year. We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission. However, first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ. While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks, the two treatment groups seemed to converge by 1 year. Longer duration of untreated psychosis was associated with lower odds of achieving remission.", "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.", "Childhood-onset schizophrenia is a rare but severe form of the disorder that is frequently treatment resistant. The psychiatrist has a limited evidence base to guide treatment, particularly as there are no trials in children comparing atypical antipsychotics, the mainstay of current treatment.\n To compare the efficacy and safety of olanzapine and clozapine, hypothesizing that clozapine would be more efficacious.\n Double-blind randomized 8-week controlled trial, with a 2-year open-label follow-up.\n National Institute of Mental Health study, January 1998 to June 2005. Patients underwent reassessment 2 years after discharge.\n Children and adolescents recruited nationally, aged 7 to 16 years, meeting unmodified DSM-IV criteria for schizophrenia, and resistant to treatment with at least 2 antipsychotics.\n After drug washout and a 1- to 3-week antipsychotic-free period, patients were randomized to treatment with clozapine (n = 12) or olanzapine (n = 13).\n The Clinical Global Impression Severity of Symptoms Scale and Schedule for the Assessment of Negative/Positive Symptoms.\n Clozapine was associated with a significant reduction in all outcome measures, whereas olanzapine showed a less consistent profile of clinical improvement. While there were moderate to large differential treatment effects in favor of clozapine, these reached significance only in the alleviation of negative symptoms from an antipsychotic-free baseline (P = .04; effect size, 0.89). Clozapine was associated with more overall adverse events. At 2-year follow-up, 15 patients were receiving clozapine with evidence of sustained clinical improvement, but additional adverse events emerged, including lipid anomalies (n = 6) and seizures (n = 1).\n While not demonstrating definitively the superiority of clozapine compared with olanzapine in treatment-refractory childhood-onset schizophrenia, the study suggests that clozapine has a more favorable profile of clinical response, which is balanced against more associated adverse events.", "The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge. Clozapine, an atypical antipsychotic drug, has long been of scientific interest, but its clinical development has been delayed because of an associated risk of agranulocytosis. This report describes a multicenter clinical trial to assess clozapine's efficacy in the treatment of patients who are refractory to neuroleptics. DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospective, single-blind trial of haloperidol (mean dosage, 61 +/- 14 mg/d) for six weeks. Patients whose condition remained unimproved were then randomly assigned, in a double-blind manner, to clozapine (up to 900 mg/d) or chlorpromazine (up to 1800 mg/d) for six weeks. Two hundred sixty-eight patients were entered in the double-blind comparison. When a priori criteria were used, 30% of the clozapine-treated patients were categorized as responders compared with 4% of chlorpromazine-treated patients. Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale, Clinical Global Impression Scale, and Nurses' Observation Scale for Inpatient Evaluation; this improvement included \"negative\" as well as positive symptom areas. Although no cases of agranulocytosis occurred during this relatively brief study, in our view, the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients.", "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." ]

[ "9915528", "10528595", "10327093", "16934640", "18325883", "2138548", "9915532", "2665802", "12677565" ]

[ "Increased efficiency and cost-effectiveness in the evaluation of the blunt abdominal trauma patient with the use of ultrasound.", "Prospective evidence of the superiority of a sonography-based algorithm in the assessment of blunt abdominal injury.", "Randomized controlled study of ultrasound therapy in the management of acute lateral ligament sprains of the ankle joint.", "Randomized controlled clinical trial of point-of-care, limited ultrasonography for trauma in the emergency department: the first sonography outcomes assessment program trial.", "A randomized controlled clinical trial of 2295 ultrasound-guided embryo transfers.", "Intracranial haemodynamics in patients with spontaneous carotid dissection. Transcranial Doppler ultrasound follow-up studies.", "Prospective, randomized evaluation of early removal of nasogastric tubes in postceliotomy trauma patients.", "Ultrasound and pulsed electromagnetic energy treatment for perineal trauma. A randomized placebo-controlled trial.", "Randomized controlled trials in pediatric surgery: could we do better?" ]

[ "The efficacy and effectiveness of ultrasound (US) in evaluating patients suspected of having blunt abdominal trauma are near that of computed tomography (CT) and diagnostic peritoneal lavage (DPL). Because no cost-effectiveness study has been reported, the purpose of this study was to demonstrate that US is more efficient and cost-effective than CT/DPL in evaluating blunt abdominal trauma. Over a 9-month period, 331 patients suspected of sustaining blunt abdominal trauma were evaluated at a Level I trauma center by US, CT, and/or DPL. Cost data and time to disposition were determined for analysis. The sensitivity, specificity, and accuracy of US were similar to those reported in previous studies. There was a significant difference in time to disposition with the US group being significantly lower (P = 0.001). The total procedural cost was 2.8 times greater for the CT/DPL group than for the US group. US is not only effective in diagnosing blunt abdominal trauma, but it is also more efficient and cost-effective than is CT/DPL.", "Although the routine use of FAST (focused assessment with sonography for trauma) in the evaluation of trauma victims is increasing, to our knowledge, a prospective comparison of contemporary adult trauma victims managed with and without FAST has not been reported in North America.\n Adult victims of blunt trauma for whom there was a suspicion of abdominal injury were managed with one of two diagnostic algorithms, FAST or no-FAST. The two algorithms were compared for diagnostic accuracy, cost, time, and delayed diagnoses.\n Among 706 patients (mean Injury Severity Score, 23), 460 were managed with FAST and 246 with no-FAST. The two groups were similar with respect to age, Injury Severity Score, prehospital time, and mortality (p = not significant). There were 3 of 460 (0.7%) delayed diagnoses in the FAST group and 4 of 246 (1.6%) in the no-FAST group (p = not significant). The diagnostic accuracy for the FAST and no-FAST algorithms was 99% and 98%, respectfully. The FAST and no-FAST algorithms led to similar rates of laparotomy, 13% and 14%, respectfully, but nonoperative management was more common in the no-FAST group (p < 0.01). The mean diagnostic cost for the FAST algorithm was $156, compared with $540 with the no-FAST algorithm (p < 0.0001) and the mean time required for diagnostic work-up was 53 minutes with the FAST algorithm, compared with 151 minutes with the no-FAST algorithm (p < 0.0001).\n This study has provided prospective evidence that a FAST-based algorithm for blunt abdominal injury was more rapid, less expensive, and as accurate as an algorithm that used computed tomography or diagnostic peritoneal lavage only. Trauma centers are encouraged to incorporate a FAST-based algorithm into their initial management of blunt trauma victims.", "To determine the efficacy of a fixed dose of ultrasound energy to treat acute lateral ligament sprains of the ankle joint.\n Double-blind randomised controlled trial.\n Accident and Emergency department of University Teaching Hospital.\n Patients presenting at Accident and Emergency with ankle injuries.\n Ultrasound or placebo, and Tubigrip.\n Pain measured with visual analogue scales, swelling using a tape measure, range of movement using a fluid-filled goniometer, and weight bearing using two scales simultaneously.\n Patients in both groups improved symptomatically. There were no statistically significant differences between groups in any outcome measure. Within groups, statistically significant differences were detected in pain perceived, and range of movement (dorsiflexion).\n At the dose and duration used, ultrasound therapy is no better than placebo in the management of lateral ligament injuries.", "Annually, 38 million people are evaluated for trauma, the leading cause of death in persons younger than 45 years. The primary objective is to assess whether using a protocol inclusive of point-of-care, limited ultrasonography (PLUS), compared to usual care (control), among patients presenting to the emergency department (ED) with suspected torso trauma decreased time to operative care.\n The study was a randomized controlled clinical trial conducted during a 6-month period at 2 Level I trauma centers. The intervention was PLUS conducted by verified clinician sonographers. The primary outcome measure was time from ED arrival to transfer to operative care; secondary outcomes included computed tomography (CT) use, length of stay, complications, and charges. Regression models controlled for confounders and analyzed physician-to-physician variability. All analyses were conducted on an intention-to-treat basis. Results are presented as mean, first-quartile, median, and third-quartile, with multiplicative change and 95% confidence intervals (CIs), or percentage with odds ratio and 95% CIs.\n Four hundred forty-four patients with suspected torso trauma were eligible; 136 patients lacked consent, and attending physicians refused enrollment of 46 patients. Two hundred sixty-two patients were enrolled: 135 PLUS patients and 127 controls. There were no important differences between groups. Time to operative care was 64% (48, 76) less for PLUS compared to control patients. PLUS patients underwent fewer CTs (odds ratio 0.16) (0.07, 0.32), spent 27% (1, 46) fewer days in hospital, and had fewer complications (odds ratio 0.16) (0.07, 0.32), and charges were 35% (19, 48) less compared to control.\n A PLUS-inclusive protocol significantly decreased time to operative care in patients with suspected torso trauma, with improved resource use and lower charges.", "We wanted to test the hypothesis that using abdominal ultrasound at the time of embryo transfer to guide replacement, improved pregnancy rates by at least 5%.\n An RCT in a large assisted conception unit. A pilot study and power calculation suggested that at least 2000 embryo transfers were required to demonstrate a difference of 5%, for a test with 80% power and Type 1 error 0.05. Randomization, data entry and analysis were arranged independently. Randomization was stratified for age and fresh/frozen embryo transfer. Analysis was by intention to treat.\n There was no difference in clinical pregnancy or live birth rates between the two groups. The clinical pregnancy rate for ultrasound-guided embryo transfer was 22% and for non-ultrasound-guided embryo transfer was 23% (odds ratio: 0.96; 95% confidence interval: 0.79-1.18).\n We set out to determine whether ultrasound-guided embryo transfer improved clinical pregnancy rates and live birth rates in assisted conception. We used an appropriately powered RCT design. We did not demonstrate a difference. This outcome is at odds with the UKs National Institute of Clinical Excellence recommendations for fertility treatment (Fertility Assessment and Treatment for People with Fertility Problems. London, UK: RCOG Press, 2004, 112.) which used a meta-analysis of four smaller trials (range 362-800 patients, totalling 2051 embryo transfers) to conclude that ultrasound should be offered. We suggest that the current Cochrane review should be updated with data from our trial and recommend that consideration is given to accounting for heterogeneity between the included trials.", "In this study 11 patients aged between 34 and 57 years with clinical and angiographic findings typical of carotid dissection were thoroughly examined with transcranial Doppler ultrasound (TCD) repeatedly during a follow-up period of 1-6 months. Stagnating blood flow velocities in the downstream middle cerebral artery (MCA) were recorded initially as well as enhanced velocities due to postischaemic hyperperfusion syndrome. MCA embolism originating from the extracranial carotid artery with or without resolution could be detected by TCD in 5 cases. TCD findings in another 2 cases pointed to haemodynamic upset. In 3 cases, clinical as well as TCD data did not allow strict differentiation between embolic and haemodynamic complications, suggesting more complex pathophysiological mechanisms as the cause of infarction. Carotid recanalization was seen in 9 cases. The follow-up investigations moreover demonstrated that intracranial haemodynamics may change from day to day in patients suffering from internal carotid artery dissection. TCD data may thus improve the understanding of pathogenetics as well as rationales for individual therapeutic intervention in this particular disease.", "The objective of this study is to compare early (24-hour) removal of nasogastric tubes (NGTs) in trauma patients who have undergone emergency celiotomy to removal based on clinical signs of return of bowel function. All trauma patients who underwent an emergency celiotomy between November 1994 and August 1997 were randomized to 24-hour NGT removal, or removal when flatus and decreased NG output indicated. Exclusion criteria included patients with duodenal or esophageal injuries, those with airway intubations that were >24 hours, or those who had undergone same-hospitalization repeat celiotomy. Gastric or severity of intestinal injury were not exclusion criteria. Failure of NGT removal was defined as pain, abdominal distention, and vomiting. Mechanisms of injury, Injury Severity Score, operative findings, NGT removal times, morbidity, laboratory data, and reasons for failure were evaluated. A total of 177 patients qualified for the study. Two patients were inappropriately randomized and subsequently excluded. Of the remaining 175 patients, 151 sustained penetrating injuries and 24 sustained blunt injuries. Of the 151 patients in the penetrating injury group, 68 were randomized to the 24-hour pull (study) group and 83 were randomized to the clinical pull (control) group. There were three failures in the study group [3 of 68 patients (4.4%)] and three failures in the control group [3 of 83 patients (3.6%)]. Of the 24 blunt injury patients, 10 were randomized to the study group and 14 were randomized to the control group. There was one failure in the study group [1 of 10 patients (10.0%)] and one failure in the control group [1 of 14 patients (7.1%)]. Overall failure rate for the study group was 5.1 per cent [(3+1)/(68+10) = 5.1%] versus 4.1 per cent for the control group. Overall failure for all patients in the study was 4.6 per cent. Injury severity score, morbidity, and lab values were not significantly different. It is safe to remove NGTs at 24 hours in most trauma patients regardless of the severity of injury (failure rate, 5.1%). The surgical dogma of the need to have an NGT in longer for blunt trauma was not revealed in this study, however, a larger study would be needed to determine this with significance.", "Ultrasound and pulsed electromagnetic energy therapies are increasingly used for perineal trauma sustained during childbirth. The study included 414 women with moderate or severe perineal trauma randomly allocated to receive active ultrasound, or active pulsed electromagnetic energy, or corresponding placebo therapies; the allocation was double-blind for each machine. Overall, more than 90% thought that treatment made their problem better. There were no clear differences between the groups in outcome either immediately after treatment, or 10 days or 3 months postpartum, other than more pain associated with pulsed electromagnetic energy treatment at 10 days. Bruising looked more extensive after ultrasound therapy but then seemed to resolve more quickly. Neither therapy had an effect on perineal oedema or haemorrhoids. The place of these new therapies in postnatal care should be clarified by further controlled trials before they become part of routine care.", "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." ]

[ "11356585", "11729030", "18162017", "9232667", "9850359", "10334524", "9404747", "10522500", "12202284" ]

[ "Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia.", "A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia.", "Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial.", "Evaluation of antitussive agents in man.", "Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma.", "Safety and efficacy of using a single agent or a phase II agent before instituting standard combination chemotherapy in previously untreated metastatic breast cancer patients: report of a randomized study--Cancer and Leukemia Group B 8642.", "Routine nebulized ipratropium and albuterol together are better than either alone in COPD. The COMBIVENT Inhalation Solution Study Group.", "Use of topical ascorbic acid and its effects on photodamaged skin topography.", "Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia." ]

[ "Evidence that the metabolism of phospholipids and polyunsaturated fatty acids (PUFA) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation. An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies. The first study was designed to distinguish between the possible effects of two different n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA, DHA or placebo for 3 months. Improvement on EPA measured by the Positive and Negative Syndrome Scale (PANSS) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS. EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures. In the second placebo-controlled study, EPA was used as a sole treatment, though the use of antipsychotic drugs was still permitted if this was clinically imperative. By the end of the study, all 12 patients on placebo, but only eight out of 14 patients on EPA, were taking antipsychotic drugs. Despite this, patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study. It is concluded that EPA may represent a new treatment approach to schizophrenia, and this requires investigation by large-scale placebo-controlled trials.", "This study determined if augmentation of neuroleptics with 3 g/day of ethyl eicosapentaenoic acid (EPA) improves symptoms and cognition in patients with schizophrenia or schizoaffective disorder.\n Eighty-seven patients meeting criteria for schizophrenia or schizoaffective disorder who had residual symptoms despite neuroleptic treatment were randomly assigned to receive either 3 g/day of ethyl EPA (N=43) or placebo (N=44) in a 16-week, double-blind supplementation trial. Assessments were performed at baseline and at weeks 1, 2, 4, 8, 12, and 16; a cognitive battery was administered at baseline and at week 16.\n No differences were found between groups in positive or negative symptoms, mood, cognition, or global impression ratings. Results were similar for the intention-to-treat (N=87) and completer (N=75) groups.\n For schizophrenia patients treated with 3 g/day of ethyl EPA, improvement in residual symptoms and cognitive impairment was no greater than for schizophrenia patients treated with placebo.", "To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP).\n We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures.\n Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all timepoints), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone.\n The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted.\n Australian Clinical Trials Registry identifier 12605000267651 (http://actr.org.au).", "Methodology to evaluate the efficacy of antitussive drugs rely largely on subjective methods and cough counts. There are few studies in cough due to natural disease especially using objective techniques. This paper presents data from a series of randomized, double blind, placebo controlled clinical trials in cough due to both chronic bronchopulmonary disease and acute upper respiratory tract infections. In these studies, cough was quantified using a standardized and validated computerized system for the acquisition and multidimensional analysis of the cough sound. Key objective parameters like cough counts, intensity, latency and total effort expended were studied. Guaiphenesin and bromhexine showed significant expectorant effects in patients with productive cough due to chronic bronchopulmonary disease. Differences were observed in speed of action, and objective and subjective measures, that probably indicate differences in drug action. More recently, three studies evaluated the antitussive drug dextromethorphan in non-productive cough due to uncomplicated upper respiratory tract infections. Reproducible cough suppressant effects were demonstrated after a single 30 mg dose using objective measures of cough counts, latency and total effort. These results establish the sensitivity and robustness of the cough quantitation methodology in the objective evaluation of cough treatments.", "Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.", "We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients.\n A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF.\n The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm.\n The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.", "We compared the long-term safety and efficacy of the combination ipratropium bromide (IB) and albuterol sulfate (ALB) inhalation solution with that of each separate component using three-times-daily administration.\n Using a parallel design, we randomized patients to receive 3.0 mg ALB, 0.5 mg IB, or the combination by small-volume nebulizer (SVN) for 85 days. Subjects were allowed to use up to two extra doses of study medication daily for control of symptoms on an as-needed basis. The main efficacy evaluation was the acute pulmonary function response to an aerosol of the maintenance study medication over the course of the investigation. Physician global evaluation, subject quality of life assessments, COPD symptom scores, and twice-daily peak expiratory flow rate (PEFR) were also assessed over the study period.\n Twenty-five centers participated in the investigation.\n We studied 652 patients with moderate to severe COPD.\n Over the course of the study, the acute spirometric response and evening PEFR values with the SVN combination of IB plus ALB were statistically significantly better compared to ALB or IB alone. The quality of life scores, physician global evaluations, symptom scores, and morning PEFR scores were unchanged over the duration of the study in all treatment groups. There was no significant difference in adverse events in the three treatment groups.\n In patients with COPD, maintenance SVN therapy with IB and ALB provides better bronchodilation than either therapy alone without increasing side effects.", "To determine the efficacy of topical ascorbic acid application in treating mild to moderate photodamage of facial skin using an objective, computer-assisted image analysis of skin surface topography and subjective clinical, photographic, and patient self-appraisal questionnaires.\n A 3-month, randomized, double-blind, vehicle-controlled study.\n Facial plastic surgery private practice.\n Nineteen evaluable volunteer sample patients aged between 36 and 72 years with Fitzpatrick skin types I, II, and III who were in good physical and mental health with mild to moderately photodamaged facial skin were considered for analysis.\n Coded, unmarked medications were randomly assigned to the left and right sides of each subject's face, one containing the active agent, topical ascorbic acid (Cellex-C high-potency serum; Cellex-C International, Toronto, Ontario), the other, the vehicle serum (Cellex-C International). Three drops (0.5 mL) of each formulation were applied daily to the randomly assigned hemifaces over the 3-month study period. Treatment assignments were not disclosed to subjects, clinicians, or personnel involved in analyzing skin replicas.\n Specific clinical parameters were evaluated and graded on a 0- to 9-point scale (0, none; 1-3, mild; 4-6, moderate; and 7-9, severe). Reference photographs were used to standardize grading criteria. Overall investigator scores were compared with baseline and graded as excellent (much improved), good (improved), fair (slightly improved), no change, or worse. Patient self-appraisal questionnaires rated the degree of improvement (much improved, improved, slightly improved, no change, or worse) and reported adverse effects (burning, stinging, redness, peeling, dryness, discoloration, itching, and rash). Standard photographs were taken at baseline, including anteroposterior and left and right oblique views to facilitate subsequent clinical evaluations, and at the end of therapy for comparison. Optical profilometry analysis was performed on the skin surface replicas of the lateral canthal (crow's feet) region, comparing baseline to end-of-study specimens. Using this computer-based system, the resulting image was digitally analyzed, and numeric values were assigned to reflect surface features. The parameters obtained included Rz, Ra, and shadows. These values provided objective data that document pretreatment and posttreatment texture changes proportional to the degree of wrinkling, roughness, and other surface irregularities.\n Optical profilometry image analysis demonstrated a statistically significant 73.7% improvement in the Ra and shadows north-south facial axis values with active treatment greater than vehicle control, as well as a trend for improvement in the Rz north-south facial axis parameter, showing a 68.4% greater improvement of active treatment vs vehicle control. Clinical assessment demonstrated significant improvement with active treatment greater than control for fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone, sallowness/yellowing, and overall features. Patient questionnaire results demonstrated statistically significant improvement overall, active treatment 84.2% greater than control. Photographic assessment demonstrated significant improvement, active treatment 57.9% greater than control.\n A 3-month daily regimen of topical ascorbic acid provided objective and subjective improvement in photodamaged facial skin. Skin replica optical profilometry is an objective method for quantification of the skin surface texture changes.", "The study investigated the efficacy and tolerability of ethyl-eicosapentaenoic acid (E-EPA) as add-on treatment in chronic, severe schizophrenia.\n A randomized, parallel-group, double-blind, placebo-controlled, fixed-dose, add-on study was conducted over 12 weeks. Forty patients with persistent symptoms after at least 6 months of stable antipsychotic treatment received E-EPA or placebo, in addition to their existing treatment.\n At 12 weeks, the E-EPA group had significantly greater reduction of Positive and Negative Syndrome Scale total scores and of dyskinesia scores than the placebo group.\n EPA may be an effective and well-tolerated add-on treatment in schizophrenia." ]

[ "18556683", "7977520", "8513962", "20883991", "8458450", "7951404", "15884262", "16963174", "7577849" ]

[ "Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial.", "Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial.", "A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis.", "Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue.", "Buserelin acetate in the treatment of pelvic pain associated with minimal and mild endometriosis: a controlled study.", "Pain of endometriosis: effects of nafarelin and danazol therapy.", "[Influence of GnRH analogue on the intensification of endometriosis symptoms and infertility treatment].", "Use of a progestogen only preparation containing desogestrel in the treatment of recurrent pelvic pain after conservative surgery for endometriosis.", "Updating the clinical experience in endometriosis--the European perspective." ]

[ "Endometriosis is associated with an inflammatory response. Hence infliximab, an anti-TNF-alpha monoclonal antibody, might relieve pain.\n A randomized placebo-controlled trial was designed with 21 women with severe pain and a rectovaginal nodule of at least 1 cm. After 1 month of observation, three infusions of infliximab (5 mg/kg) or placebo were given. Surgery was performed 3 months later and follow-up continued for 6 months. The primary end-point was pain (dysmenorrhea, deep dyspareunia and non-menstrual pain) rated at each visit by the clinician and on a daily basis by the patient who in addition scored pain by visual analog pain scale and analgesia intake. Secondary end-points included the volume of the endometriotic nodule, pelvic tenderness and the visual appearance of endometriotic lesions at laparoscopy.\n Pain severity decreased during the treatment by 30% in both the placebo (P < 0.001) and infliximab groups (P < 0.001). However, no effect of infliximab was observed for any of the outcome measures. After surgery, pain scores decreased in both groups to less than 20% of the initial value.\n Infliximab appears not to affect pain associated with deep endometriosis. Treatment is associated with an important placebo effect. After surgery, pain decreases to less than 20%. Trials registration number ClinicalTrials.gov: NCT00604864.", "Our purpose was to investigate the efficacy of postsurgical treatment with nafarelin in women with advanced endometriosis.\n Eligible for trial were women < or = 38 years old with unexplained infertility with or without chronic pelvic pain and stage III or IV endometriosis according to the American Fertility Society, revised, classification who underwent laparotomy as first surgical treatment for debulking or radical surgery of endometriotic lesions. Patients were assigned according to a randomization list to nasal nafarelin, 400 micrograms/day (36 subjects) or placebo nasal spray (39 subjects) for 3 months. Pelvic pain was assessed before first surgery and at the 12-month follow-up visit in women with pelvic pain by means of a multidimensional score system and a 10-point linear pain scale.\n No marked differences in pain scores emerged among women allocated to different treatments. The mean reduction of the multidimensional score was 3.6 and 4.0, respectively, in women allocated to nafarelin and placebo and of the 10-point linear scale scores was 7.0 and 6.9. These differences were not statistically significant. Within 1 year from randomization, of the 36 women allocated to nafarelin and the 39 allocated to placebo, seven (19%) and seven (18%), respectively, became pregnant.\n This study suggests that medical treatment with nafarelin does not markedly improve pelvic pain and short-term reproductive prognosis in women with stages III and IV endometriosis.", "To evaluate the efficacy of goserelin versus a low-dose cyclic oral contraceptive (OC) in improving pelvic pain in women with endometriosis and to compare recurrence of symptoms during follow-up.\n Open-label, randomized trial.\n University hospital endometriosis center.\n Fifty-seven women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis.\n Six-month treatment with goserelin depot (n = 29) or a low-dose cyclic OC (n = 28) followed by 6-month follow-up.\n Variation in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale.\n At 6 months of treatment, a significant reduction in deep dyspareunia was observed in both groups, with goserelin superior to the OC at linear analog scale assessment. Nonmenstrual pain was diminished on both scales without differences between treatments. Women taking the OC experienced a significant reduction in dysmenorrhea. At the end of follow-up, symptoms reappeared without differences in severity between the groups.\n Low-dose cyclic OCs may be a valuable alternative for the treatment of dysmenorrhea and nonmenstrual pain associated with endometriosis. Symptoms recurred in most subjects 6 months after drug withdrawal.", "To compare efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena) with depot GnRH analogue (GnRH-a; gosareline acetate; Zoladex) on endometriosis-related chronic pelvic pain (CPP) in patients with severe endometriosis during 12 months.\n Prospective, randomized, controlled study.\n The reproductive endocrinology unit of a tertiary, research and education hospital.\n Forty women with severe endometriosis (revised The American Fertility Society [AFS] classification >40) and endometriosis-related CPP and control groups were enrolled in the study.\n The patients were treated with either LNG-IUS (n = 20) or GnRH-a (n = 20). The GnRH-a dose was repeated every 4 weeks for 24 weeks.\n Scores of CPP were evaluated using a visual analogue scale (VAS) and total endometriosis severity profile (TESP).\n The TESP score decreased in the LNG-IUS group at first, third, and sixth month follow-up visits, whereas at the 12th month follow-up visit, the TESP scores were increased to values similar to pretreatment values. Although the VAS score had no significant alteration during the follow-up period in the LNG-IUS group, the GnRH-a group showed a significant decrease in the VAS score and TESP score at the end of 1 year. The LNG-IUS treatment showed a lower patient satisfaction.\n Both treatment modalities showed comparable effectiveness in the treatment of CPP-related endometriosis.\n Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "To evaluate the changes of pain symptoms induced by buserelin acetate, a gonadotropin-releasing hormone agonist, in a group of patients with endometriosis.\n Thirty-five infertile patients with one or more of the following symptoms (dysmenorrhea, pelvic pain, deep dyspareunia, and endometriosis stage I or II) were allocated randomly to treatment with buserelin acetate 1,200 micrograms/d IN for 6 months (n = 19) or expectant management (n = 16). Pain symptoms were recorded by the women themselves using a questionnaire that included two scales for pain evaluation: one analogue and one multidimensional. The treated and untreated patients were followed for a minimum of 18 and 12 months from the time of randomization, respectively.\n Buserelin acetate markedly reduced dysmenorrhea, pelvic pain, and dyspareunia during the treatment and also for the 12 subsequent months. During follow-up of the expectant management group, dysmenorrhea resolved in 19% (3/16) of the cases, and pelvic pain did not recur after diagnostic laparoscopy in one of the three women affected nor did deep dyspareunia in two of the five who reported the symptom before laparoscopy.\n Buserelin acetate induced a significant improvement of pain symptoms that persisted in approximately half of the patients even after withdrawal of the drug. However, symptoms associated with endometriosis showed a spontaneous remission in approximately one fifth of the untreated patients.", "To compare the efficacy of nafarelin acetate with danazol in the treatment of dysmenorrhea, dyspareunia, and pelvic pain associated with endometriosis.\n Prospective, randomized double-blind controlled study. PATIENTS, SETTING, TREATMENTS: Two hundred thirteen patients aged 18 to 48 with laparoscopically confirmed pelvic endometriosis and dysmenorrhea, dyspareunia or pelvic pain were randomly assigned to 6 months of treatment with either nafarelin acetate 800 micrograms per day or 400 micrograms per day, or danazol 800 micrograms per day.\n The percentage of patients with dysmenorrhea, dyspareunia or pelvic pain before treatment who still had these symptoms after 6 months of treatment and 6 months following completion of treatment. RESULTS [table: see text]\n Nafarelin acetate and danazol both provided significant relief of dysmenorrhea, dyspareunia, and pelvic pain during treatment and for 6 months following treatment in women with endometriosis.", "The aim of this study was to evaluate the influence of the treatment with oral doses of 50 mg GnRH analogue on the intensification of endometriosis symptoms and infertility amongst women with evident symptoms of endometriosis in comparison with placebo group. A group of 34 women at the age from 18 to 45 were introduced into the study. The inclusion criteria for investigated population contained: endometriosis symptoms, endometriosis diagnosed by laparoscopy, its surgical or pharmacological treatment, negative pregnancy test score and regular menses. The patients were divided into 2 groups: investigated group and control group. Women completed \"Diary\" every day in which they estimated main endometriosis symptoms: dysmenorrhea, dyspareunia, pelvic pain and vaginal bleeding (according to Pain Grading Scale). The intensification of dysmenorrhea and vaginal bleeding was reduced in the investigated group in comparison with control one. These differences were statistically significant. Although the extremity of dyspareunia was decreased in two groups, this correlation was statistically significant only in the investigated group. Pelvic pain evaluation showed that its level was lower in the investigated group (p > 0.05). It was found that 11 women (investigated group) and 5 women (control group) got pregnant after the period of 12-week treatment.\n GnRH analogues have an efficient influence on the reduction of endometriosis symptoms. GnRH analogues could be used in the management of infertility.", "To assess the effect of a new progestin progestogen only pill (desogestrel) versus an oral contraceptive in the treatment of recurrent endometriosis.\n A randomized prospective clinical study. A group of women with endometriosis (n=40) who showed recurrent dysmenorrhea and/or pelvic pain after conservative surgery, and did not desire a pregnancy. Continuous treatment for 6 months with desogestrel (75 microg/d) (n=20) versus a combined oral contraceptive (ethinyl estradiol 20 microg plus desogestrel 150 microg) (n=20) was performed.\n A significant improvement of both pelvic pain and dysmenorrhea was observed following each type of treatment (P<0.001). The use of desogestrel progestogen only pill was associated with a breakthrough bleeding in 20% patients, while a significant body weight increase was observed in 15% after oral contraceptive.\n Both desogestrel and an oral estro-progestinic were effective, safe and low cost therapy of pain symptoms after endoscopic surgery for endometriosis, the former showing an impact on breakthrough bleeding, the later an incidence on body weight increase.", "In a large, double-blind, multicentre study, 269 patients with confirmed endometriosis were randomly allocated to receive either danazol (200 mg twice daily; n = 137) or gestrinone (2.5 mg twice weekly; n = 132) for 6 months. The two groups were comparable in terms of the staging of endometriosis by the American Fertility Society (1979) score. After the sixth month of treatment, repeat laparoscopy was performed. Clinical assessment, haematological and biochemical investigations were carried out during the 6 months of treatment and for a further 12 months' follow-up and are compared between the two groups. A total of 15 patients from the gestrinone group, including four patients with hirsutism, and 17 patients from the danazol group, including six patients with headache, withdrew because of adverse symptoms. An additional 22 patients, including 10 from the gestrinone group and 12 from the danazol group withdrew because of lack of efficacy, pregnancy, elevated hepatic function tests or for reasons unrelated to the trial. Total American Fertility Society scoring showed an improvement of 73.3% in 101 patients receiving gestrinone and 72.7% in 99 patients receiving danazol. The results showed a significant reduction in the severity of dysmenorrhoea by the third month in the danazol group and at 6 months in both groups. There was a significant (P < 0.001) increase in weight observed in both groups during treatment. Overall, the tolerability of danazol and gestrinone was good; however, significantly more patients with gestrinone complained of hirsutism while significantly more with danazol complained of leg cramps. During the 12 months of follow-up, mild, moderate or severe degrees of lower abdominal pain, dysmenorrhoea and deep dyspareunia all fluctuated, with no statistically significant increase in frequency in either group." ]

[ "17388666", "16919803", "9388397", "18645518", "16849391", "19716639", "10028980", "12182264", "19996048" ]

[ "Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe.", "A brief individualized computer-delivered sexual risk reduction intervention increases HIV/AIDS preventive behavior.", "Randomised, controlled, community-level HIV-prevention intervention for sexual-risk behaviour among homosexual men in US cities. Community HIV Prevention Research Collaborative.", "Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study.", "A randomized control trial of Internet-delivered HIV prevention targeting rural MSM.", "Empowering sex workers in India to reduce vulnerability to HIV and sexually transmitted diseases.", "Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group.", "Reducing STD and HIV risk behavior of substance-dependent adolescents: a randomized controlled trial.", "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." ]

[ "HIV-1 control in sub-Saharan Africa requires cost-effective and sustainable programmes that promote behaviour change and reduce cofactor sexually transmitted infections (STIs) at the population and individual levels.\n We measured the feasibility of community-based peer education, free condom distribution, income-generating projects, and clinic-based STI treatment and counselling services and evaluated their impact on the incidence of HIV-1 measured over a 3-y period in a cluster-randomised controlled trial in eastern Zimbabwe. Analysis of primary outcomes was on an intention-to-treat basis. The income-generating projects proved impossible to implement in the prevailing economic climate. Despite greater programme activity and knowledge in the intervention communities, the incidence rate ratio of HIV-1 was 1.27 (95% confidence interval [CI] 0.92-1.75) compared to the control communities. No evidence was found for reduced incidence of self-reported STI symptoms or high-risk sexual behaviour in the intervention communities. Males who attended programme meetings had lower HIV-1 incidence (incidence rate ratio 0.48, 95% CI 0.24-0.98), and fewer men who attended programme meetings reported unprotected sex with casual partners (odds ratio 0.45, 95% CI 0.28-0.75). More male STI patients in the intervention communities reported cessation of symptoms (odds ratio 2.49, 95% CI 1.21-5.12).\n Integrated peer education, condom distribution, and syndromic STI management did not reduce population-level HIV-1 incidence in a declining epidemic, despite reducing HIV-1 incidence in the immediate male target group. Our results highlight the need to assess the community-level impact of interventions that are effective amongst targeted population sub-groups.", "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.", "Community-level interventions may be helpful in population-focused HIV prevention. If members of populations at risk of HIV infection who are popular with other members can be engaged to advocate the benefits of behaviour change to peers, decreases in risk behaviour may be possible. We assessed a community-level intervention to lower the risk of HIV infection, focusing on men patronising gay bars in eight small US cities.\n We used a randomised community-level field design. Four cities received the intervention and four control cities did not. Participants were men from each city who went to gay bars. Men completed surveys about their sexual behaviour on entering the bars during 3-night periods at baseline and at 1-year follow-up. In the control cities, HIV educational materials were placed in the bars. In the intervention cities, we recruited popular homosexual men in the community and trained them to spread behaviour-change endorsements and recommendations to their peers through conversation.\n Population-level of risk behaviour decreased significantly in the intervention cities compared with the control cities at 1-year follow-up, after exclusion of surveys completed by transients and men with exclusive sexual partners in a city-level analysis, in the intervention cities we found a reduction in the mean frequency of unprotected anal intercourse during the previous 2 months (baseline 1.68 occasions; follow-up 0.59: p = 0.04) and an increase in the mean percentage of occasions of anal intercourse protected by condoms (baseline 44.7%; follow-up 66.8%, p = 0.02). Increased numbers of condoms taken from dispensers in intervention-city bars corroborated risk-behaviour self-reports.\n Popular and well-liked members of a community who systematically endorse and recommend risk-reduction behaviour can influence the sexual-risk practices of others in their social networks. Natural styles of communication, such as conversations, brought about population-level changes in risk behaviour.", "To evaluate the feasibility, fidelity, and effectiveness of a human immunodeficiency virus (HIV) prevention intervention delivered to HIV-infected patients by counselors during routine clinical care in KwaZulu-Natal, South Africa.\n A total of 152 HIV-infected patients, aged 18 years and older, receiving clinical care at an urban hospital in South Africa, were randomly assigned to intervention or standard-of-care control counselors. Intervention counselors implemented a brief risk reduction intervention at each clinical encounter to help patients reduce their unprotected sexual behavior. Self-report questionnaires were administered at baseline and 6 months to assess number of unprotected sex events in previous 3 months.\n Intervention was delivered in 99% of routine patient visits and included a modal 8 of 8 intervention steps. Although HIV-infected patients in both conditions reported more vaginal and anal sex events at 6-month follow-up than at baseline, patients who received the counselor-delivered intervention reported a significant decrease over time in number of unprotected sexual events. There was a marginally significant increase in these events among patients in the standard-of-care control condition.\n A counselor-delivered HIV prevention intervention targeting HIV-infected patients seems to be feasible to implement with fidelity in the South African clinical care setting and effective at reducing unprotected sexual behavior.", "The Internet may be important for delivering human immunodeficiency virus (HIV) risk reduction to men who have sex with men (MSM) in rural areas. This randomized control trial (RCT) tested the acceptability and efficacy of an Internet-delivered HIV risk-reduction intervention. Two modules include a conversation between an HIV-negative man and an HIV-positive man, with interactive graphics. Ninety men were randomly assigned to intervention or wait-list control and 79% completed the study. An 'intent-to-treat' model was used. HIV/acquired immune deficiency syndrome (AIDS) knowledge, self-efficacy and outcome expectancies increased after participating in the intervention, and changes were maintained at 1-week follow-up. Participants said they would participate again. This RCT provides support for the acceptability and efficacy of the Internet for delivering HIV prevention messages to rural MSM.", "The Sonagachi Project was initiated in Kolkata, India in 1992 as a STD/HIV intervention for sex workers. The project evolved to adopt strategies common to women's empowerment programs globally (i.e., community mobilization, rights-based framing, advocacy, micro-finance) to address common factors that support effective, evidence-based HIV/STD prevention. The Sonagachi model is now a broadly diffused evidence-based empowerment program. We previously demonstrated significant condom use increases among female sex workers in a 16 month replication trial of the Sonagachi empowerment intervention (n=110) compared to a control community (n=106) receiving standard care of STD clinic, condom promotion, and peer education in two randomly assigned rural towns in West Bengal, India (Basu et al., 2004). This article examines the intervention's impacts on 21 measured variables reflecting five common factors of effective HIV/STD prevention programs to estimate the impact of empowerment strategies on HIV/STD prevention program goals. The intervention which was conducted in 2000-2001 significantly: 1) improved knowledge of STDs and condom protection from STD and HIV, and maintained STD/HIV risk perceptions despite treatment; 2) provided a frame to motivate change based on reframing sex work as valid work, increasing disclosure of profession, and instilling a hopeful future orientation reflected in desire for more education or training; 3) improved skills in sexual and workplace negotiations reflected in increased refusal, condom decision-making, and ability to change work contract, but not ability to take leave; 4) built social support by increasing social interactions outside work, social function participation, and helping other sex workers; and 5) addressed environmental barriers of economic vulnerabilities by increasing savings and alternative income, but not working in other locations, nor reduced loan taking, and did not increase voting to build social capital. This study's results demonstrate that, compared to narrowcast clinical and prevention services alone, empowerment strategies can significantly impact a broader range of factors to reduce vulnerability to HIV/STDs.", "The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities.\n This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios.\n The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses.\n We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors.", "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.", "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." ]

[ "9870617", "17227922", "16788315", "7835575", "11413109", "15015606", "20009750", "15362027", "16426990" ]

[ "The non-specific effect of endolymphatic sac surgery in treatment of Meniere's disease: a prospective, randomized controlled study comparing \"classic\" endolymphatic sac surgery with the insertion of a ventilating tube in the tympanic membrane.", "A randomized controlled trial of laparoscopic nissen fundoplication versus proton pump inhibitors for treatment of patients with chronic gastroesophageal reflux disease: One-year follow-up.", "Elective administration in infants of low-dose recombinant activated factor VII (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not shorten time to chest closure or reduce blood loss and need for transfusions: a randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy.", "Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn's disease. Italian Cooperative Study Group.", "Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease.", "Palliative management of malignant rectosigmoidal obstruction. Colostomy vs. endoscopic stenting. A randomized prospective trial.", "The influence of mechanical bowel preparation in elective lower colorectal surgery.", "Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial.", "Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial." ]

[ "A prospective, randomized study was carried out comparing the effect of two surgical modalities in the treatment of patients with Meniere's disease: insertion of an endolymphatic sac shunt and insertion of a ventilating tube in the tympanic membrane. A total of 29 patients, 12 males and 17 females, age 27-71 years, were operated on in two ear, nose and throat (ENT) departments. Of these patients, 15 had an endolymphatic shunt inserted and 14 had a ventilating tube inserted in the tympanic membrane. Postoperative follow-up was carried out in the department in which the patients had not been operated. The severity of the disease was scored pre- and postoperatively, and the results evaluated under the guidelines of the Committee on Hearing and Equilibrium (1995) for the diagnosis and evaluation of therapy in Meniere's disease. The patients in both groups had a statistically significant reduction in dizzy spells, measured 6 and 12 months postoperatively, and there was no difference between the groups. The pathophysiological explanation for the reduction in dizzy spells in each of the treatment modalities is debatable and the effect is non-specific. The patients' hearing and tinnitus were statistically unaffected by the treatment in both groups, though 2 patients in the shunt group developed severe hearing loss (anacusis/70 dB).", "A randomized controlled trial conducted in patients with gastroesophageal reflux disease compared optimized medical therapy using proton pump inhibitor (n = 52) with laparoscopic Nissen fundoplication (n = 52). Patients were monitored for 1 year. The primary end point was frequency of gastroesophageal reflux dis-ease symptoms. Surgical patients had improved symptoms, pH control, and overall quality of life health index after surgery at 1 year compared with the medical group. The overall gastroesophageal reflux disease symptom score at 1 year was unchanged in the medical patients, but improved in the surgical patients. Fourteen patients in the medical arm experienced symptom relapse requiring titration of the proton pump inhibitor dose, but 6 had satisfactory symptom remission. No surgical patients required additional treatment for symptom control. Patients controlled on long-term proton pump inhibitor therapy for chronic gastroesophageal reflux disease are excellent surgical candidates and should experience improved symptom control after surgery at 1 year.", "We investigated the effectiveness of prophylactic administration of recombinant activated factor VII (rFVIIa) for cardiopulmonary bypass surgery in children under 1 year old with congenital heart disease (CHD) in a double-blinded, placebo-controlled study. The rFVIIa dose was 40 microg/kg and all patients also received standard haemostatic replacement therapy. The primary endpoint was the time to chest closure from neutralization of heparin with protamine sulphate as this could be most objectively and accurately measured during surgery. Secondary endpoints were volumes of transfused blood, platelet concentrates and fresh-frozen plasma. All adverse events were recorded. In the intention-to-treat analysis there were 76 patients (40 in rFVIIa group and 36 in placebo group). The demographics and severity of CHD were similar in both groups. No benefit of rFVIIa prophylaxis was found in the time to chest closure, which was significantly prolonged in the rFVIIa group (rFVIIa mean +/- SE, 98.8 +/- 27.27 versus 55.3 +/- 29.15, P = 0.0263). In the 41 patients available for a follow-up visit 6 weeks after discharge, the chest closure time was also prolonged in the rFVIIa group (P = 0.0515). There were no significant differences in the secondary endpoints. Adverse events were similar in both groups.", "Recurrence of lesions of Crohn's disease of the ileum within 1 year after so-called curative resection was well documented by endoscopy in 73%-93% of cases. This study investigated the efficacy of mesalamine in reduction of endoscopic recurrence after surgery.\n In a double-blind, multicenter clinical trial, 87 patients were treated with 3 g/day mesalamine (Pentasa) or with placebo within 1 month after surgery. After 12 months of treatment, severity of endoscopic lesions was recorded with a five-point score; when it was not possible to reach the anastomosis by endoscopy, a barium enema was performed.\n Seventeen clinical relapses (seven in the mesalamine group) were recorded. After 12 months, the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group (chi 2, 13.5; P < 0.008). The overall rate of severe recurrence (score of 3-4 on endoscopy or radiological documentation) was 24% in the mesalamine group and 56% in the placebo group (chi 2, 8.57; P < 0.004; difference 32%; 95% confidence interval, 22-52). The odds ratio for active treatment was 4.1.\n This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's disease.", "New lesions of Crohn's disease occur early after ileal or ileocolonic resection and ileocolonic anastomosis. We performed a double blind controlled trial to evaluate the safety and tolerance of recombinant human interleukin 10 (IL-10; Tenovil) in subjects operated on for Crohn's disease. We also assessed the effect of Tenovil in preventing endoscopic recurrence 12 weeks after surgery.\n Patients with Crohn's disease who underwent curative ileal or ileocolonic resection and primary anastomosis were randomised within two weeks after surgery to receive subcutaneous Tenovil 4 microg/kg once daily (QD) (n=22) or 8 microg/kg twice weekly (TIW) (n=21), or placebo (QD or TIW) (n=22). An ileocolonoscopy was performed after 12 weeks of treatment.\n Compliance was excellent. The most frequently observed adverse events were mild and moderate in severity and equally distributed across treatment groups. Thirty seven patients in the pooled Tenovil group and 21 patients in the pooled placebo group were evaluable by endoscopy. At 12 weeks, 11 of 21 patients (52%) in the placebo group had recurrent lesions compared with 17 of 37 patients (46%) in the Tenovil group (ns). The incidence of severe endoscopic recurrence was similar in both groups (9%).\n Tenovil treatment for 12 consecutive weeks in patients with Crohn's disease after intestinal resection was safe and well tolerated. No evidence of prevention of endoscopic recurrence of Crohn's disease by Tenovil was observed.", "Colostomy was the palliative treatment of choice in patients with malignant unresectable rectosigmoid obstruction. Palliative endoscopic treatment of malignant rectosigmoid obstruction by endoluminal self-expanding metallic stents is nowadays a well-established procedure.\n Twenty-two patients, referred for treatment with diagnosis of malignant obstruction of the rectosigmoid region presenting an advanced unresectable stage, were enrolled. Patients were randomly assigned into two treatment groups (endoscopic stenting vs colostomy) according to random-number tables. The length of procedure, morbidity and mortality rate, canalization of the gastrointestinal tract, restoration of oral intake and hospital stay were assessed.\n Endoscopic group: The median length of procedure was 36 minutes. No death was observed. None of the patients reported complications. All patients resumed bowel function within 24 hours. The restoration of oral intake was achieved one day after stent placement. The median hospital stay was 2.6 days. Colostomy group: The median length of the operation was 75.4 minutes. No mortality was reported. In 1 patient (9.1%) stoma prolapse was observed 3 days after the operation. Canalization of the gastrointestinal tract was restored when colostomy was opened (on postoperative day 3). All patients were able to resume oral feedings on postoperative day 3. The median hospital stay was 8.1 days.\n There were no statistically significant differences between the 2 groups concerning morbidity and mortality. Endoscopic stenting was significantly more effective concerning operative time, restoration of bowel function and oral intake and median hospitalization. Our results would suggest that endoscopically placed metal stents offer an effective alternative to surgical palliation in patients suffering from unresectable malignant rectosigmoid obstruction.", "This study evaluates the effects of mechanical bowel preparation (MBP) on anastomosis below the peritoneal verge and questions the influence of MBP on anastomotic leakage in combination with a diverting ileostomy in lower colorectal surgery.\n In a previous large multicenter randomized controlled trial MBP has shown to have no influence on the incidence of anastomotic leakage in overall colorectal surgery. The role of MBP in lower colorectal surgery with or without a diverting ileostomy remains unclear.\n This study is a subgroup analysis of a prior multicenter (13 hospitals) randomized trial comparing clinical outcome of MBP versus no MBP. Primary end point was the occurrence of anastomotic leakage and secondary endpoints were septic complications and mortality.\n Total of 449 Patients underwent a low anterior resection with a primary anastomosis below the peritoneal verge. The incidence of anastomotic leakage was 7.6% for patients who received MBP and 6.6% for patients who did not. Significant risk factors for anastomotic leakage were the American Society of Anesthesiologists-classification (P = 0.005) and male gender (P = 0.007). Of total, 48 patients received a diverting ileostomy during initial surgery; 27 patients received MBP and 21 patients did not. There were no significant differences regarding septic complications and mortality between both groups.\n MBP has no influence on the incidence of anastomotic leakage in low colorectal surgery. Furthermore, omitting MBP in combination with a diverting ileostomy has no influence on the incidence of anastomotic leakage, septic complications, and mortality rate.", "No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn's disease. The aim of the current trial was to compare 6-mercaptopurine (6-MP) and mesalamine with placebo for the prevention of clinical, endoscopic, and radiographic recurrence of Crohn's disease after resection and ileocolic anastomosis.\n Five centers randomized 131 patients to receive 6-MP (50 mg), mesalamine (3 g), or placebo daily in a double-blind, double-dummy trial. Patients had clinical assessments at 7 weeks and then every 3 months; colonoscopy at 6, 12, and 24 months; and small bowel series at 12 and 24 months. End points were clinical, endoscopic, and radiographic recurrence rates at 24 months.\n Clinical recurrence rates (intent to treat) by life-table analysis at 24 months were 50% (95% confidence interval [CI], 34%-68%), 58% (95% CI, 41%-75%), and 77% (95% CI, 61%-91%) in patients receiving 6-MP, mesalamine, and placebo, respectively. Endoscopic recurrence rates were 43% (95% CI, 28%-63%), 63% (95% CI, 47%-79%), and 64% (95% CI, 46%-81%), and radiographic recurrence rates were 33% (95% CI, 19%-54%), 46% (95% CI, 29%-66%), and 49% (95% CI, 30%-72%), respectively. 6-MP was more effective than placebo ( P < 0.05) at preventing clinical and endoscopic recurrence over 2 years. Patient withdrawals resulted in 69% of the study population evaluable for the clinical recurrence end point.\n 6-MP, 50 mg daily, was more effective than placebo at preventing postoperative recurrence of Crohn's disease and should be considered as a maintenance therapy after ileocolic resection.", "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." ]

[ "15654136", "9688391", "8299789", "10099977", "7558391", "10615885", "19531445", "8822431", "7962385" ]

[ "A randomised prospective trial of intrauterine insemination versus timed intercourse in superovulated cycles with clomiphene.", "Controlled ovarian hyperstimulation and intrauterine insemination for treating male subfertility: a controlled study.", "Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles.", "The clinical efficacy of low-dose step-up follicle stimulating hormone administration for treatment of unexplained infertility.", "Intrauterine insemination of washed spermatozoa for treatment of oligozoospermia.", "Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis.", "A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial.", "Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility.", "Clinical pregnancy and male subfertility; the ESHRE multicentre trial on the treatment of male subfertility. European Society of Human Reproduction and Embryology." ]

[ "Despite its wide use, the benefits of intrauterine insemination (IUI), its over timed intercourse (TI) in couples with unexplained infertility is a matter of debate. Studies in Indian couples with unexplained infertility showing benefit of IUI over TI are not available. The present study was done with the objective of comparing TI and IUI with husband's sperm in couples with unexplained infertility undergoing superovulation with clomiphene.\n A total of 140 couples with unexplained infertility were subjected to controlled ovarian hyperstimulation (COH) with clomiphene and prospectively randomized to receive either TI (group A) or IUI (group B). Complete follow up was available for 113 couples only.\n The pregnancy rate and cycle fecundity rate after COH/TI was 41 and 8.8 per cent and after COH/IUI 18 and 3.4 per cent respectively. The difference was statistically not significant.\n The findings of the present study showed that in women with unexplained infertility addition of IUI to ovulation induction does not improve conception rates. COH/TI can help to achieve good results and save the expense and discomfort due to a invasive procedure.", "In this randomized crossover trial we investigated whether the use of controlled ovarian hyperstimulation with low-dose human menopausal gonadotrophin in couples with male subfertility leads to a higher probability of conception when intrauterine insemination (IUI) is applied. We also investigated whether the efficacy of IUI in natural or stimulated cycles was related to the severity of male subfertility. Seventy-four couples completed 308 treatment cycles. Thirteen pregnancies occurred after IUI in a natural cycle (pregnancy rate per completed cycle: 8.4%) and 21 after IUI in a stimulated cycle (pregnancy rate per completed cycle: 13.7%). The difference between the two treatment modalities was not statistically significant. The efficacy of IUI in stimulated cycles was related to the severity of the semen defect. In couples with a total motile sperm count < 10 x 10(6), ovarian stimulation did not improve treatment outcome, while it did in couples with a total motile sperm count > or = 10 x 10(6). Compared with the expected chance of conceiving spontaneously without treatment, both natural and stimulated cycles improved the probability of conception. We conclude that, for the group as a whole, ovarian stimulation did not improve the probability of conception. However, in couples with less severe semen defects, ovarian stimulation did improve the probability of conception.", "To test the hypothesis that in couples undergoing IUI, actively managed cycles using clomiphene citrate (CC) stimulation, ultrasound monitoring, and hCG timing will result in increased pregnancy rate (PR) per cycle compared with unstimulated urinary LH-timed cycles.\n Fifty-six couples with unexplained infertility (n = 26) or male factor infertility (n = 30) participated in the study.\n Tertiary academic medical center.\n Prospective, randomized, crossover. Couples were randomized initially to one of the two study groups (treatment A: LH-timed IUI; treatment B: CC-stimulated, hCG-timed IUI). If no pregnancy occurred, each couple alternated between the two regimens during subsequent cycles, up to a total of four cycles.\n Twenty-nine couples completed the study and the analysis of 95 cycles revealed that among the male factor infertility group, one pregnancy occurred during the 26 cycles of each treatment group (PR per cycle of 3.9% for both treatment groups). In contrast, among the unexplained infertility group, there was a marked difference in the effect of treatments. During treatment A only one pregnancy occurred in 20 cycles (PR of 5% per cycle) whereas during treatment B, six pregnancies occurred in 23 cycles (PR of 26.1% per cycle).\n If IUI is chosen as the treatment modality in unexplained infertility, the addition of active ovulation management that includes CC stimulation, ultrasound monitoring of folliculogenesis, and hCG timing of ovulation increases the PR per cycle. In couples with male infertility, PR per cycle is low and is apparently not affected by the addition of active ovulation management.", "The present study was designed to compare the clinical efficacy of low-dose step-up follicle stimulating hormone (FSH) administration with conventional FSH protocol (FSH was injected daily starting with a dose of 150 IU), both combined with intrauterine insemination (IUI), for the treatment of unexplained infertility. A total of 97 unexplained infertility couples was randomly assigned to one or other of the two treatment groups, either conventional FSH with IUI (48 patients) or low-dose step-up FSH with IUI (49 patients), and only the first treatment cycle was evaluated in each protocol. The difference in pregnancy rates per cycle was not statistically significant between the low-dose FSH group and the conventional group [seven of 49 (14.3%) and seven of 48 (14.6%) respectively]. A significant reduction in the incidence of ovarian hyperstimulation syndrome (OHSS) was observed in the low-dose group (8.3% versus 27.1%, P < 0.05). The incidence of moderate OHSS requiring hospitalization was reduced significantly in the low-dose group (low-dose 0% versus conventional 16.7%, P < 0.01). However, the low-dose protocol did not completely prevent multiple pregnancies. Our results suggest that the low-dose step-up FSH treatment appeared to be useful for the treatment of unexplained infertility because of the high pregnancy rates and the significant decrease in the incidence of OHSS.", "Efficacy of intrauterine insemination (IUI) using washed spermatozoa for treatment of oligozoospermia was evaluated by a prospective randomized study in 50 couples, using LH-timed natural intercourse in the alternate menstrual cycles as a control. The quality of spermatozoa in terms of their concentration and motility before and after sperm washing was compared. Sperm motility increased significantly after sperm preparation but the number of sperm was reduced. Eight pregnancies occurred in 253 cycles of IUI with washed spermatozoa and clomiphene citrate-stimulated cycles (3.16% per cycle). Only one patient conceived in 242 LH-timed natural intercourse cycles (0.41% per cycle). Compared with LH-timed natural intercourse, IUI provided a significantly improved pregnancy rate. When the sperm count was < 5 x 10(6) per ml, no pregnancy occurred with the IUI method. Therefore, IUI is a of rather limited usefulness when the sperm quality is very poor. Few complications occurred after IUI, but included slight cervical contact bleeding and mild abdominal discomfort and/or cramps. In conclusion, IUI should be considered as a useful and relatively non-invasive therapeutic modality for treating caused by moderate oligozoospermia (> 5 x 10(6)/ml), when sexual intercourse fails.", "Couples affected by idiopathic subfertility or male subfertility have an estimated spontaneous conception rate of about 2% per cycle. Although various infertility treatments are available, counselling of a couple in their choice of treatment is difficult because of the lack of consistent data from good-quality comparative studies. We compared the results of treatment with intrauterine insemination (IUI) with those of in-vitro fertilisation (IVF), and did a cost-effectiveness analysis.\n In a prospective, randomised, parallel trial, 258 couples with idiopathic subfertility or male subfertility were treated for a maximum of six cycles of either IUI in the spontaneous cycle (IUI alone), IUI after mild ovarian hyperstimulation, or IVF. The primary endpoint was a pregnancy resulting in at least one livebirth after treatment. Cost-effectiveness based on real costs was studied by Markov chain analysis.\n 86 couples were assigned IUI alone, 85 IUI plus ovarian hyperstimulation, and 87 IVF. Ten couples dropped out before treatment began. Although the pregnancy rate per cycle was higher in the IVF group than in the IUI groups (12.2% vs 7.4% and 8.7%, respectively; p=0.09), the cumulative pregnancy rate for IVF was not significantly better than that for IUI. Couples in the IVF group were more likely than those in the IUI groups to give up treatment before their maximum of six attempts (37 [42%] drop-outs vs 13 [15%] and 14 [16%], respectively; p<0.01). The woman's age was the only factor that influenced a couple's chance of success. IUI was a more cost-effective treatment than IVF (costs per pregnancy resulting in at least one livebirth 8423-10661 Dutch guilders [US$4511-5710] for IUI vs 27409 Dutch guilders [US$14679] for IVF).\n Couples with idiopathic or male subfertility should be counselled that IUI offers the same likelihood of successful pregnancy as IVF, and is a more cost-effective approach. IUI in the spontaneous cycle carries fewer health risks than does IUI after mild hormonal stimulation and is therefore the first-choice treatment.", "To determine the value of gonadotropin/intrauterine insemination (FSH/IUI) therapy for infertile women aged 21-39 years.\n Randomized controlled trial.\n Academic medical center associated with a private infertility center.\n Couples with unexplained infertility.\n Couples were randomized to receive either conventional treatment (n=247) with three cycles of clomiphene citrate (CC)/IUI, three cycles of FSH/IUI, and up to six cycles of IVF or an accelerated treatment (n=256) that omitted the three cycles of FSH/IUI.\n The time it took to establish a pregnancy that led to a live birth and cost-effectiveness, defined as the ratio of the sum of all health insurance charges between randomization and delivery divided by the number of couples delivering at least one live-born baby.\n An increased rate of pregnancy was observed in the accelerated arm (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.00-1.56) compared with the conventional arm. Median time to pregnancy was 8 and 11 months in the accelerated and conventional arms, respectively. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. Average charges per delivery were $9,800 lower (95% CI, $25,100 lower to $3,900 higher) in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of $2,624 per couple for accelerated treatment and 0.06 more deliveries.\n A randomized clinical trial demonstrated that FSH/IUI treatment was of no added value.\n Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "The aim of this prospective randomized controlled study was to determine the possible role of ovulation induction with intrauterine insemination (IUI) in the treatment of unexplained infertility. A total of 100 patients were randomized to receive ovulation induction with or without IUI. All patients were treated with long-course gonadotrophin-releasing hormone analogue (GnRHa), starting in the luteal phase, and exogenous follicle stimulating hormone (FSH) to induce follicular growth. Ovulation was induced using human chorionic gonadotrophin and timed intercourse (TI) was advised 24-48 h later or IUI was effected 36-48 h later. Both the cycle fecundities (21.8 and 8.5%) and the cumulative ongoing pregnancy rates after three cycles (42 and 20%) were significantly higher (P < 0.03) in the IUI group than in the TI group respectively. This is a clear indication that ovulation induction with IUI is an effective treatment method for unexplained infertility, but ovulation induction with TI has a negligible impact in this large group of patients.", "Ovulation induction alone, and ovulation induction in conjunction with one of four assisted procreation methods [intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF)] were tested as a treatment for male infertility in a prospective randomized trial. The trial when completed had generated data on 499 cycles from 346 patients. There was overwhelming evidence that some form of assisted procreation was beneficial, when compared to the spontaneous natural conception rate, which is generally assumed to be between 0.01 and 0.02 for male infertility. There was also firm evidence that IUI, GIFT or IVF (mean per cycle pregnancy rate 0.212) were superior to the remaining two treatments of IPI and ovulation induction alone (mean per cycle pregnancy rate 0.068). Duration of infertility and a diagnosis of endometriosis were the most important (adverse) pre-treatment factors detected." ]

[ "6931470", "387151", "8104468", "406212", "3788652", "7032224", "3446307", "6349256", "2870944" ]

[ "Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate.", "High dose flupenthixol decanoate in chronic schizophrenia.", "The decanoates of flupenthixol and clopenthixol in the treatment of chronic schizophrenic in-patients. Implications for community psychiatry.", "Clinical and social comparison of fluphenazine decanoate and flupenthixol decanoate in the community maintenance therapy of schizophrenia.", "Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison.", "A depot neuroleptic withdrawal study. A controlled study of the clinical effects of the withdrawal of depot fluphenazine decanoate and depot flupenthixol decanoate in chronic schizophrenic patients.", "Double-blind comparison of half-dose and standard-dose flupenthixol decanoate in the maintenance treatment of stabilised out-patients with schizophrenia.", "Comparative double-blind study of flupenthixol decanoate and fluphenazine decanoate in the treatment of patients relapsing in a schizophrenic symptomatology.", "A comparative trial of depot pipothiazine." ]

[ "Clopenthixol decanoate and flupenthixol palmitate, both depot neuroleptics belonging to the thioxanthene group, were studied during double-blind conditions for 12 months using four week intervals between injections. The 60 patients included in the study were chronic schizophrenics and treated as outpatients after earlier admission to hospital and rehabilitation training periods. They had all been treated with depot neuroleptics in the last three years and they had been free from relapse for at least 15 months. The main aim with this trial was to study the two depot drugs during maintenance treatment conditions in an outpatient setting. Ten patients dropped out, 7 because of unsatisfactory effect, mainly because only limited dose levels were accepted according to the design. In spite of the earlier long lasting neuroleptic treatment and the good social adaptation in this schizophrenic subgroup there was observed a symptom decrease in all the rating scales even in these symptom poor patients. This improvement in psychopathology with optimal results after half a year seems to be a combined result of the efficient neuroleptics tested and careful monitoring of the drug.", "In a double-blind trial, female 'drug-resistant' chronic schizophrenic in-patients were given high dose or standard dose flupenthixol decanoate for 13 weeks. Plasma flupenthixol levels showed a five-fold interindividual variation, but were consistently higher with the high dose. Analysis of final scores showed no statistically significant differences between groups with regards to mental state, ward behaviour and extrapyramidal side-effects. When compared with pre-trial scores, the extrapyramidal side-effects worsened significantly in the high dose patients and social withdrawal decreased in the standard dose patients. The mental state of a sub-group of patients, possibly drug resistant for pharmacokinetic reasons, improved significantly on the high dose over the 13 weeks.", "Vagrant chronic schizophrenic subjects in a stable untreated state received in-patient treatment with either Flupenthixol decanoate or Clopenthixol decanoate. Both drugs were found to be significantly effective and well tolerated. The apparent better response to Flupenthixol decanoate was seen as dose-dependent. The findings and their implications for Community Psychiatry, particularly in developing countries are discussed.", "The clinical and social effects of flupenthixol decanoate and fluphenazine decanoate were compared in the maintenance treatment of a population of chronic schizophrenic out-patients over a period of 9 months. The results failed to show significant difference between the treatments, and in particular, reports suggesting specific advantages for flupenthixol decanoate in alleviating the negative symptoms of apathy, anergia and depression in chronic schizophrenics were not confirmed. It seems that chronic schizophrenic patients who are well established on one depot preparation are unlikely to be benefited by being changed to the alternative.", "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.", "A double-blind withdrawal trial in 41 chronic schizophrenic outpatients on neuroleptics was carried out during 6 months. Long-acting neuroleptics (fluphenazine decanoate or flupenthixol decanoate) were used in comparison with placebo to determine the value in maintenance therapy. Most patients had a rather low maintenance dose, about 12.5-25 mg fluphenazine decanoate or 20-40 mg flupenthixol decanoate every third week. Relapse was often characterized by a return of the dame symptoms as the patient had during his first schizophrenic attack. Drugs were significantly more effective than placebo in preventing relapse and readmission to hospital. 62% relapsed in the placebo groups as compared with 27% in the drug group. All patients on active substance and without relapse during the controlled study had their treatment discontinued for 24 months in an open follow-up investigation. This resulted in relapse of all patients but one, i.e. a final relapse frequency of 97%. A significant weight decrease was observed in the placebo group. The risk of withdrawal is discussed.", "A double-blind controlled trial of 50% dose reduction in maintenance treatment in stable out-patients with low BPRS scores and good social function shows a significantly higher relapse rate in the low-dose group at 12 months (P less than 0.05). After an interval of 24-36 months from dose reduction, 56-76% had experienced a relapse and 76-79% had resumed their former dosage. No clear advantage was shown for the lower dose in either a reduction of side-effects or improved social function, but a reduced prevalence or lower rate of symptom emergence for tardive dyskinesia was suggested.", "Thirty-two chronic schizophrenics who had relapsed entered a double-blind randomised study and were followed-up for 2 years with the intention of measuring any difference in therapeutic effect and side effects between flupenthixol decanoate and fluphenazine decanoate. No differences could be seen as regards the global effect or the effect on the schizophrenic symptomatology during the first 6 months. After 1 year of treatment flupenthixol decanoate showed a trend towards a better effect on schizophrenic symptomatology. A corresponding result was seen for the depressive symptoms. There were no differences in the appearance of side effects. The need for additional neuroleptics in the initial phase seemed to be identical for both drugs. A possible slow antipsychotic effect with flupenthixol decanoate is probably due to the administered dose being somewhat low (in the present study approximately 31 mg flupenthixol corresponding to 27 mg fluphenazine). This suggests that flupenthixol should have been given in a somewhat higher dose (25 mg fluphenazine decanoate corresponding to 40 mg flupenthixol decanoate).", "Thirty-nine chronic schizophrenic patients were selected for a 12-month double-blind evaluation of the effectiveness of pipothiazine palmitate (PPT) and flupenthixol decanoate (FPX) in the maintenance management of their illness. Allocation was at random and, in order to allow constant injection intervals, the patients typically received every 2 weeks either 40 mg of flupenthixol decanoate or alternating injections of 100 mg of pipothiazine palmitate and placebo. At monthly intervals the patients were assessed using both a battery of rating scales (which included the Brief Psychiatric Rating Scale (BPRS), the Extrapyramidal Symptoms Rating Scale (EPS] and a general side-effects evaluation. At 3-monthly intervals they were also rated on the Comprehensive Psychiatric Rating Scale (CPRS) and the Zung Depression Scale. Haematological and biochemical tests were performed every 3 months. Both drugs provided good control of psychotic symptoms and side-effects were not troublesome. No substantial difference was detected on the CPRS and the Zung scales. There was a trend in favour of PPT on the BPRS survey, detectable at 6 months and reaching statistical significance by 12 months. We conclude that the PPT regime is at least as effective as the FPX treatment and probably more so. It is possible that even longer periods of control could be obtained with PPT." ]

[ "16137351", "16227328", "10556125", "15065730", "18585831", "15065822", "20723631", "10859037", "16941367" ]

[ "Intrapulmonary percussive ventilation in acute exacerbations of COPD patients with mild respiratory acidosis: a randomized controlled trial [ISRCTN17802078].", "Clinical efficacy of anti-pneumococcal vaccination in patients with COPD.", "Acute respiratory failure in patients with severe community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventilation.", "Improving physician coverage of pneumococcal vaccine: a randomized trial of a telephone intervention.", "Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease.", "Additive preventive effect of influenza and pneumococcal vaccines in elderly persons.", "Effectiveness of pneumococcal polysaccharide vaccine against pneumonia and cost analysis for the elderly who receive seasonal influenza vaccine in Japan.", "Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial.", "Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study." ]

[ "We hypothesized that the use of intrapulmonary percussive ventilation (IPV), a technique designed to improve mucus clearance, could prove effective in avoiding further deterioration in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) with mild respiratory acidosis.\n The study was performed in a medical intensive care unit of a university hospital. Thirty-three patients with exacerbations of COPD with a respiratory frequency >or= 25/min, a PaCO2 > 45 Torr and 7.35 <or= pH <or= 7.38 were included in the study. Patients were randomly assigned to receive either standard treatment (control group) or standard treatment plus IPV (IPV group). The IPV group underwent two daily sessions of 30 minutes performed by a chest physiotherapist through a full face mask. The therapy was considered successful when both worsening of the exacerbation and a decrease in pH to under 7.35, which would have required non-invasive ventilation, were avoided.\n Thirty minutes of IPV led to a significant decrease in respiratory rate, an increase in PaO2 and a decrease in PaCO2 (p < 0.05). Exacerbation worsened in 6 out of 17 patients in the control group versus 0 out of 16 in the IPV group (p < 0.05). The hospital stay was significantly shorter in the IPV group than in the control group (6.8 +/- 1.0 vs. 7.9 +/- 1.3 days, p < 0.05).\n IPV is a safe technique and may prevent further deterioration in patients with acute exacerbations of COPD with mild respiratory acidosis.", "A study was undertaken to evaluate the clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV) in immunocompetent patients with chronic obstructive pulmonary disease (COPD).\n A randomised controlled trial was carried out in 596 patients with COPD of mean (SD) age 65.8 (9.7) years, 298 of whom received PPV. The main outcome was radiographically proven community acquired pneumonia (CAP) of pneumococcal or unknown aetiology after a mean period of 979 days (range 20-1454).\n There were 58 first episodes of CAP caused by pneumococcus or of unknown aetiology, 25 in the intervention group and 33 in the non-intervention group. Kaplan-Meier survival curves for CAP did not show significant differences between the intervention and non-intervention arms (log rank test = 1.15, p = 0.28) in the whole group of patients. The efficacy of PPV in all patients was 24% (95% CI -24 to 54; p = 0.333). In the subgroup aged <65 years the efficacy of PPV was 76% (95% CI 20 to 93; p = 0.013), while in those with severe functional obstruction (forced expiratory volume in 1 second <40%) it was 48% (95% CI -7 to 80; p = 0.076). In younger patients with severe airflow obstruction the efficacy was 91% (95% CI 35 to 99; p = 0.002). There were only five cases of non-bacteraemic pneumococcal CAP, all in the non-intervention group (log rank test = 5.03; p = 0.025). Multivariate analysis gave a hazard ratio for unknown and pneumococcal CAP in the vaccinated group, adjusted for age, of 0.20 (95% CI 0.06 to 0.68; p = 0.01).\n PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction. No differences were found among the other groups of patients with COPD.", "In uncontrolled studies, noninvasive positive pressure ventilation (NPPV) was found useful in avoiding endotracheal intubation in patients with acute respiratory failure (ARF) caused by severe community-acquired pneumonia (CAP). We conducted a prospective, randomized study comparing standard treatment plus NPPV delivered through a face mask to standard treatment alone in patients with severe CAP and ARF. Patients fitting the American Thoracic Society criteria for severe CAP were included in presence of ARF (refractory hypoxemia and/or hypercapnia with acidosis). Exclusion criteria were: severe hemodynamic instability, requirement for emergent cardiopulmonary resuscitation, home mechanical ventilation or oxygen long-term supplementation, concomitant severe disease with a low expectation of life, inability to expectorate or contraindications to the use of the mask. Fifty-six consecutive patients (28 in each arm) were enrolled, and the two groups were similar at study entry. The use of NPPV was well tolerated, safe, and associated with a significant reduction in respiratory rate, need for endotracheal intubation (21% versus 50%; p = 0.03), and duration of intensive care unit (ICU) stay (1.8 +/- 0.7 d versus 6 +/- 1.8 d; p = 0.04). The two groups had a similar intensity of nursing care workload, time interval from study entry to endotracheal intubation, duration of hospitalization, and hospital mortality. Among patients with chronic obstructive pulmonary disease (COPD), those randomized to NPPV had a lower intensity of nursing care workload (p = 0.04) and improved 2-mo survival (88.9% versus 37.5%; p = 0.05). We conclude that in selected patients with ARF caused by severe CAP, NPPV was associated with a significant reduction in the rate of endotracheal intubation and duration of ICU stay. A 2-mo survival advantage was seen in patients with COPD.", "Improved pneumococcal vaccine (PPV) immunization for seniors is a national goal of the Medicare program. This study examined whether adding a simple telephone follow-up to an existing mailed physician performance feedback under the Medicare program would increase the impact on billed pneumococcal immunizations. Medicare fee-for-service claims data were used to select New York primary care physicians with high volume (n = 732) or African-American serving (n = 329) practices. All practices received mailed feedback on their 1999 Medicare practice specific PPV coverage rates, along with educational materials and offers of assistance. Practices were also randomized to receive telephone calls directing attention to the mailing and further promoting improvements in PPV coverage or no active follow-up. Physicians randomized to telephone follow-up showed significantly higher rates of practice specific PPV coverage in 2000 than those receiving the routine mailing only, and 27% vs. 17% (p = 0.01) of high volume physicians and 34% vs. 22% (p = .052) of African American serving physicians achieved at least a 5% increase in their cumulative PPV claims coverage. This study concludes that telephone follow-up is an effective and straightforward method to enhance the impact of practice specific feedback to promote improvements in Medicare PPV immunization. However, improved methods may be needed to induce a large percentage of physicians to change.", "To determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV+IV group (n=87) or an IV group (n=80). The number of patients with CLD experiencing infectious acute exacerbation (P=0.022), but not pneumonia (P=0.284), was significantly lower in the PV+IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P=0.037). In patients with CLD, the Kaplan-Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P=0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P=0.019), but not during the second year (P=0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period.", "In 1999, all individuals > or = 65 yrs of age (n=258,754) in Stockholm County, Sweden, were offered influenza and pneumococcal vaccination in a prospective study on the effectiveness of these vaccines in reducing the need for hospital treatment and death due to influenza, pneumonia and invasive pneumococcal disease (IPD). Data on hospitalisation and mortality during 1 yr were obtained from the administrative database in Stockholm County Council. Vaccination was performed in 124,702 (48%) subjects; 72,107 had both vaccines, 29,346 only had the influenza vaccine and 23,249 only had the pneumococcal vaccine. Compared with the unvaccinated cohort, a lower incidence of hospitalisation for all endpoint diagnoses was seen in vaccinated persons. An additive effectiveness of vaccination was seen when both vaccines were given, with a reduction of hospital admissions for influenza (37%), pneumonia (29%) and IPD (44%). In-hospital mortality for pneumonia was significantly lower in those who received both vaccines, than in unvaccinated persons. To conclude, vaccination with influenza and pneumococcal vaccines together was effective in reducing the need for hospital admission for influenza and pneumonia. There was a strong indication that pneumococcal vaccination alone, was effective not only in the prevention of invasive pneumococcal disease, but also of pneumonia overall, although to a low degree.", "To determine the clinical efficacy and cost-saving effect of pneumococcal polysaccharide vaccine (PPV) against community-acquired pneumonia (CAP), an open-label, randomized clinical trial was conducted involving 786 Japanese subjects older than 65 years of age receiving a routine influenza vaccine during the 2-year period. Study subjects were randomly assigned to either a PPV group (n=394) or to a non-PPV group (n=392). The incidence, admission and the medical cost for all-cause pneumonia were compared between these two groups. PPV vaccination significantly reduced the incidence of admission for all-cause pneumonia for subjects older than 75 years of age (41.5%, P=0.039) and for those who had difficulty walking (62.7%, P=0.005), but not for all study subjects older than 65 years of age (P=0.183), for the 2-year period. The Kaplan-Meier survival curves for subjects who had difficulty walking free from all-cause pneumonia demonstrated a significant difference (P=0.0146) between the two groups. PPV vaccination significantly reduced medical costs for all study subjects during the first year period (P=0.027). Our present data demonstrated that PPV was effective for all-cause pneumonia for study subjects older than 75 years of age, although the effect was not significant for all study subjects older than 65 years of age.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "Within the intensive-care unit, non-invasive ventilation (NIV) can prevent the need for intubation and the mortality associated with severe episodes of chronic obstructive pulmonary disease (COPD). The aim of this study was to find whether the introduction of NIV, early after the admission on a general respiratory ward, was effective at reducing the need for intubation and the mortality associated with acute exacerbations of COPD.\n We did a prospective multicentre randomised controlled study comparing NIV with standard therapy in patients with mild to moderate acidosis. NIV was administered on the ward with a simple non-invasive ventilator and a standardised predefined protocol. Patients were recruited from 14 UK hospitals over 22 months.\n 236 patients were recruited, 118 received standard therapy alone and 118 additional NIV. The two groups had similar characteristics at enrolment. The use of NIV significantly reduced the need for intubation as defined by the failure criteria. 32/118 (27%) of the standard group failed compared with 18/118 (15%) of the NIV group (p=0.02). In-hospital mortality was also reduced by NIV, 24/118 (20%) died in the standard group compared with 12/118 (10%) in the NIV group (p=0.05). In both groups pH, PaCO2, and respiratory rate improved at 4 h (p<0.01). However, NIV led to a more rapid improvement in pH in the first hour (p=0.02) and a greater fall in respiratory rate at 4 h (p=0.035). The duration of breathlessness was also reduced by NIV (p=0.025).\n The early use of NIV for mildly and moderately acidotic patients with COPD in the general ward setting leads to more rapid improvement of physiological variables, a reduction in the need for invasive mechanical ventilation (with objective criteria), and a reduction in in-hospital mortality.", "The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended for elderly persons and persons who are at high risk of infection. However, the effectiveness of the 23-valent PPV remains controversial. We assessed the effectiveness of this vaccine in older adults.\n A prospective cohort study was conducted from January 2002 through April 2005; it included all community-dwelling individuals aged >or=65 years who were assigned to 1 of 8 primary health care centers in Tarragona, Spain (11,241 subjects). The primary outcomes were invasive pneumococcal disease, pneumococcal pneumonia, overall pneumonia rate, and death due to pneumonia. All cases were validated by a check of the clinical records. The association between pneumococcal vaccination and the risk of each outcome was evaluated by means of multivariate Cox proportional hazard models, adjusted for age, sex, comorbidity, immunocompetence, and influenza vaccine status.\n Pneumococcal vaccination was associated with significant reductions in the risk of hospitalization for pneumonia (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.59-0.92) and in the overall pneumonia rate (HR, 0.79; 95% CI, 0.64-0.98). The incidence of invasive pneumococcal disease was low (64 cases per 100,000 person-years), and a considerable protective effect against invasive pneumococcal disease did not attain statistical significance (HR, 0.60; 95% CI, 0.22-1.65). However, the vaccine showed a significant effectiveness of 45% to prevent pneumococcal pneumonia (HR, 0.55; 95% CI, 0.34-0.88). Finally, vaccination was associated with a significant 59% reduction in the risk of death due to pneumonia among vaccinated subjects (HR, 0.41; 95% CI, 0.23-0.72).\n These results indicate that the 23-valent PPV effectively prevented pneumococcal pneumonia (with or without bacteremia) and decreased the rates of overall pneumonia and of mortality due to pneumonia in older adults, providing new arguments for systematic vaccination in the elderly population." ]

[ "21698991", "278700", "11985192", "20848004", "22300651", "16304443", "18086027", "22736448", "19341577" ]

[ "Occlusal caries prevention in high and low risk schoolchildren. A clinical trial.", "Clinical effectiveness of an autopolymerized fissure sealant after 2 years.", "Evaluation of non-invasive treatment applied to occlusal surfaces.", "Caries-preventive efficacy and retention of a resin-modified glass ionomer cement and a resin-based fissure sealant: a 3-year split-mouth randomised clinical trial.", "Caries-preventive effect of sealants produced with altered glass-ionomer materials, after 2 years.", "Sealant and fluoride varnish in caries: a randomized trial.", "Comparing the caries-preventive effect of two fissure sealing modalities in public health care: a single application of glass ionomer and a routine resin-based sealant programme. A randomized split-mouth clinical trial.", "Randomized trial on fluorides and sealants for fissure caries prevention.", "Effectiveness of a glass ionomer cement used as a pit and fissure sealant in recently erupted permanent first molars." ]

[ "To evaluate the caries-preventive effect of a resin-modified glass-ionomer cement used as occlusal sealant (Vitremer) compared with fluoride varnish (Duraphat) application on occlusal surfaces of permanent first molars (OSPFM) in 6-8 year-old schoolchildren (n=268) at high (HR) and low (LR) caries risk.\n The children were followed-up for 24 months after being systematically allocated into six groups as follows: Control Groups HRC and LRC: children receiving oral health education (OHE) every 3 months; Groups HRV and LRV: children receiving OHE plus varnish application biannually; and Groups HRS and LRS: children receiving OHE plus a single sealant application . The baseline and follow-up examinations were performed by the same calibrated dentist under natural light, using CPI probes and mirrors, after toothbrushing and air-drying. The DMFS was used to record dental caries, in addition to the detection of initial lesions (IL). Data analysis was performed with two primary outcome measures: DMF and DMF+ IL on the OSPFM.\n After 24 months, only the HRS group showed statistically lower DMF and DMF+IL increments on OSPFM compared with HRC group. HRV group did not differ from HRC and HRS groups. For LR groups, no statistical difference (P> 0.05) was observed among the treatments.", "The clinical effectiveness of Delton fissure sealant was studied in 205 children, ages 6--10 years (mean age 71/2). 993 children in grades 1, 2, 3 and 4 were screened and subjects were selected if there was evidence of previous dental caries in the mouth, and a pair of contralateral maxillary or mandibular first permanent molar teeth were free of caries. Two pedodontists independently examined the children in a mobile van equipped with two operatories, and each applied sealants to approximately half of the subjects. After 11 months, in 186 subjects there were 10 sealants partially lost, five experimental teeth carious or filled and 53 control teeth carious or filled. After 24 months, in 175 subjects there were four sealants completely lost, 12 sealants partially lost, 11 experimental teeth carious or filled and 89 control teeth carious or filled. Consequently, sealant retention was 92% after 11 months and 85% after 24 months. Percent effectiveness in caries reduction was 90% after 11 months and 88% after 2 years.", "The purpose of this study was to evaluate the efficacy of non-invasive methods of treatment for active incipent occlusal caries. Anamnesis, professional prophylaxis, and visual inspection were used to classify 250 Brazilian pre-school-children. First permanent decayed molars (n=98) from thirty-one subjects (6 years+ 6 months) were selected and divided into three groups. Group 1: fissure sealants with resin-modified glass ionomer - Vitremer (n=29); Group 2: fluoride varnish -Duraphat (n=36) and control group: tooth brushing and 0.2 percent NaF weekly mouthwashes (n=33). Four clinical evaluations were carried out over three, six, nine, and twelve months. Caries activity and progression were observed through clinical and radiographic evaluation. The results were analyzed by Fisher=s Exact test. After twelve months, the results showed 100 percent of arrestment of caries activity for Group 1, 83.3 percent for group 2, and 72.7 percent for control group. At the same time, the results showed 0 percent of caries progression for group 1, 5.5 percent for Group 2, and 6.1 percent for control group. Group 1 showed a better inactivation property than the other groups (p<0.05). There were no statistically significant differences in caries progression among these groups (p>0.05). It was concluded that this non-invasive methods were able to arrest the progression of occlusal caries, but fissure sealant showed better results in controlling caries activity.", "This prospective clinical trial compared the retention rate and caries-preventive efficacy of two types of sealant modalities over a 3-year period.\n Using a split-mouth randomised design, 1280 sealants were randomly applied on sound permanent second molars of 320 young patients aged between 12 and 16 years. Half of the teeth (n = 640) were sealed with a resin-modified glass ionomer cement (RMGIC) (Vitremer™, 3M ESPE) and the other half (n = 640) with a conventional light-cure, resin-based fissure sealant (LCRB) (Fluoroshield®, Dentsply Caulk). Teeth were evaluated at baseline, 6-, 12-, 18-, 24-, 30- and 36-month intervals with regard to retention and new caries development.\n On the sealed occlusal surfaces after 3 years, 5.10% of RMGIC and 91.08% of LCRB sealants were totally intact and 6.37% of RMGIC and 7.65% of LCRB sealants were partially intact. New caries lesions were found in 20.06% of RMGIC sealed occlusal surfaces, compared to 8.91% for LCRB sealants.\n The findings of the present clinical study suggest that RMGIC should be used only as a transitional sealant that can be applied to newly erupting teeth throughout the eruptive process, whereas LCRB sealants are used to successfully prevent occlusal caries lesions once an effective rubber dam can be achieved. It can be concluded that there are differences between the RMGIC and LCRB sealants over a 3-year period in terms of the retention rate and caries-preventive efficacy. RMGIC can serve as a simple and economic sealing solution, however provisional. Due to its poor retention rate, periodic recalls are necessary, even after 6 months, to eventually replace the lost sealant.", "The aim of the present study was to investigate the caries-preventive effect of sealants produced with a high-viscosity glass-ionomer with an elevated powder-liquid ratio (ART), of having energy added to this glass-ionomer, and that of glass-carbomer, in comparison to that of resin composite sealants.\n The randomized controlled trial covered 407 children, with a mean age of 8 years. At a school compound three dentists placed sealants in pits and fissures of high caries-risk children. Evaluation by two independent evaluators was conducted after 0.5, 1 and 2 years. The Kaplan-Meier survival method, ANOVA and t-test were used in analyzing the data.\n 1352 first permanent molars were sealed. 6.6% of children and 6.8% of sealants dropped out within 2 years. 27 re-exposed pits and fissures, 20 in occlusal and 7 in smooth surfaces, in 25 children, developed a dentin carious lesion. The cumulative survival of dentin carious lesion-free pits and fissures in the glass-carbomer sealant group was statistically significantly lower (97.4%) than those in the high-viscosity glass-ionomer with energy supplied (99%) and the resin-composite (98.9%) sealant groups. There was no statistically significant difference in the cumulative survival of dentin carious lesion-free pits and fissures, between the high-viscosity glass-ionomer with (99%) and without (98.3%) energy supplied sealant groups, after 2 years.\n The survival of dentin carious lesion-free pits and fissures was high in all sealant types. More dentin carious lesions were observed in the glass-carbomer sealant group.\n Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.", "Little is known about the effect of discontinuation of sealant or fluoride varnish. The purpose of this study was to compare sealant with fluoride varnish in the prevention of occlusal caries in permanent first molars of children over a nine-year period: 4 yrs for program evaluation plus 5 yrs of discontinuation. A clinical trial was conducted on three groups of six- to eight-year-old schoolchildren: a control group (n = 45); a group (n = 37) in which sealant was applied and reapplied up to 36 mos; and a group (n = 38) in which fluoride varnish was applied and re-applied up to 42 mos. Percent caries reduction was studied in these initially healthy molars with complete occlusal eruption: 129 (control), 113 (sealant), and 129 (varnish) molars met inclusion criteria. Of these, 76.7%, 26.6%, and 55.8% had developed occlusal caries at 9 yrs, which implies caries reductions of 65.4% (SE = 8.5%) for sealants vs. control and 27.3% (SE = 10.2%) for varnish vs. control. Furthermore, the varnish program was not effective during the discontinuation period.", "The aim of this study was to compare the caries-preventive effect of two types of sealant modalities and to evaluate whether the caries-preventive effect is related to sealant retention. A hypothesis was tested in which a glass ionomer sealant, once applied to the occlusal surface, was able to protect the fissure from caries even if the sealant appeared lost at visual inspection.\n A 3-year randomized split-mouth trial evaluating two sealant modalities was performed at a public health centre in Finland. A chemically curing glass ionomer cement (GIC) and light-curing resin-based (RB) sealant material were applied randomly to the permanent second molars. Sealant application as a routine treatment procedure was carried out to 599 children in the age group of 12-16 years. Caries rate of the sealed teeth and sealant retention with both materials were analysed by a modified McNemar's test. The effectiveness, rate difference, and relative risk with both sealant materials were measured.\n The difference in caries rate between the two modalities was highly significant. When compared to the GIC sealant method, the effectiveness of RB sealant method was 74.1% and the rate difference 3.2% (95% CI 1.44%, 4.98%). The relative risk for RB-sealed surfaces vs. GIC-sealed surfaces of having detectable dentin caries was 0.26 (95% CI 0.12, 0.57). The retention rate of sealants was higher with RB than GIC (P < 0.001). The effectiveness of the retention rate for RB sealants was 94.8% and the rate difference 87.2% (95% CI 83.86%, 90.50%). The relative risk during the 3-year study period of having a defective or lost RB sealant was 0.052 (95% CI 0.036, 0.075) when compared to having a defective or lost GIC sealant.\n It is concluded that in preventing dentin caries a RB sealant programme including resealing when necessary was more effective than a single application of GIC. The original hypothesis was thus falsified.", "To investigate the effectiveness of topical fluorides in preventing fissure caries, we conducted a randomized controlled trial with parallel groups. In total, 501 children (1,539 molars, 3,078 sites), mean age 9.1 years, who had at least one sound permanent first molar with deep fissures or fissures with signs of early caries were recruited. They were randomly allocated among four groups: (1) resin sealant, single placement; (2) 5% NaF varnish, semi-annual application; (3) 38% silver diamine fluoride (SDF) solution, annual application; and (4) placebo control. Follow-up examinations were conducted every 6 months by a masked examiner. After 24 months, 485 children (97%) were examined. Proportions of pit/fissure sites with dentin caries in the sealant, NaF, SDF, and control groups were 1.6%, 2.4%, 2.2%, and 4.6%, respectively. A multi-level logistic regression analysis accounting for the effects of data clustering and confounding factors showed that fissures in any of the three treatment groups had significantly lower risks of carious cavity development into dentin than did controls (p < 0.05). We concluded that placement of resin sealant, semi-annual application of NaF varnish, and annual application of SDF solution are all effective in preventing pit and fissure caries in permanent molars (ClinicalTrials.gov number CT01446107).", "This study's purpose was to evaluate the caries-preventive effect of a glass ionomer cement (GIC) used as an occlusal sealant on recently erupted permanent first molars.\n A double-blind, randomized, controlled, clinical trial was undertaken that included 36 5- to 8-year-olds (and 92 permanent first molars) who were randomly allocated to the test group (GIC) or the control group (auto-polymerized resin-based sealant [RBS]). The Mann-Whitney test was used to compare the number of new carious or filled occlusal surfaces in the 2 groups.\n After 6 months, 1 occlusal surface in the test group and 2 occlusal surfaces in the control group showed carious lesions (P=.15). In the fifth year of follow-up, 2 occlusal surfaces in the test group and 7 occlusal surfaces in the control group were filled or carious (P=.42), and the mean number of sealed surfaces that became carious or filled was 0.2 (95% confidence interval [CI]=0.02-0.70) for the GIC-sealed teeth and 0.6 (95% CI=0.20-1.30) for the RBS-sealed teeth (P=.30).\n High-viscosity glass ionomer cement can provide some level of protection against dental caries when used as a dental sealant in newly erupted permanent first molars." ]

[ "17473138", "9450711", "9723823", "9310565", "12701945", "12876092", "11277147", "9676673", "2304219" ]

[ "Commercially funded and United States-based research is more likely to be published; good-quality studies with negative outcomes are not.", "Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials.", "Bias in reporting clinical trials.", "Publication bias: evidence of delayed publication in a cohort study of clinical research projects.", "Publication bias and meta-analyses: a practical example.", "Factors associated with failure to publish large randomized trials presented at an oncology meeting.", "Publication bias in presentations to the Annual Scientific Congress.", "Positive-outcome bias and other limitations in the outcome of research abstracts submitted to a scientific meeting.", "A cohort study of summary reports of controlled trials." ]

[ "Prior studies implying associations between receipt of commercial funding and positive (significant and/or pro-industry) research outcomes have analyzed only published papers, which is an insufficiently robust approach for assessing publication bias. In this study, we tested the following hypotheses regarding orthopaedic manuscripts submitted for review: (1) nonscientific variables, including receipt of commercial funding, affect the likelihood that a peer-reviewed submission will conclude with a report of a positive study outcome, and (2) positive outcomes and other, nonscientific variables are associated with acceptance for publication.\n All manuscripts about hip or knee arthroplasty that were submitted to The Journal of Bone and Joint Surgery, American Volume, over seventeen months were evaluated to determine the study design, quality, and outcome. Analyses were carried out to identify associations between scientific factors (sample size, study quality, and level of evidence) and study outcome as well as between non-scientific factors (funding source and country of origin) and study outcome. Analyses were also performed to determine whether outcome, scientific factors, or nonscientific variables were associated with acceptance for publication.\n Two hundred and nine manuscripts were reviewed. Commercial funding was not found to be associated with a positive study outcome (p = 0.668). Studies with a positive outcome were no more likely to be published than were those with a negative outcome (p = 0.410). Studies with a negative outcome were of higher quality (p = 0.003) and included larger sample sizes (p = 0.05). Commercially funded (p = 0.027) and United States-based (p = 0.020) studies were more likely to be published, even though those studies were not associated with higher quality, larger sample sizes, or lower levels of evidence (p = 0.24 to 0.79).\n Commercially funded studies submitted for review were not more likely to conclude with a positive outcome than were nonfunded studies, and studies with a positive outcome were no more likely to be published than were studies with a negative outcome. These findings contradict those of most previous analyses of published (rather than submitted) research. Commercial funding and the country of origin predict publication following peer review beyond what would be expected on the basis of study quality. Studies with a negative outcome, although seemingly superior in quality, fared no better than studies with a positive outcome in the peer-review process; this may result in inflation of apparent treatment effects when the published literature is subjected to meta-analysis.", "Medical evidence may be biased over time if completion and publication of randomized efficacy trials are delayed when results are not statistically significant.\n To evaluate whether the time to completion and the time to publication of randomized phase 2 and phase 3 trials are affected by the statistical significance of results and to describe the natural history of such trials.\n Prospective cohort of randomized efficacy trials conducted by 2 trialist groups from 1986 to 1996.\n Multicenter trial groups in human immunodeficiency virus infection sponsored by the National Institutes of Health.\n A total of 109 efficacy trials (total enrollment, 43708 patients).\n Time from start of enrollment to completion of follow-up and time from completion of follow-up to peer-reviewed publication assessed with survival analysis.\n The median time from start of enrollment to publication was 5.5 years and was substantially longer for negative trials than for results favoring an experimental arm (6.5 vs 4.3 years, respectively; P<.001; hazard ratio for time to publication for positive vs negative trials, 3.7; 95% confidence interval [CI], 1.8-7.7). This difference was mostly attributable to differences in the time from completion to publication (median, 3.0 vs 1.7 years for negative vs positive trials; P<.001). On average, trials with significant results favoring any arm completed follow-up slightly earlier than trials with nonsignificant results (median, 2.3 vs 2.5 years; P=.045), but long-protracted trials often had low event rates and failed to reach statistical significance, while trials that were terminated early had significant results. Positive trials were submitted for publication significantly more rapidly after completion than were negative trials (median, 1.0 vs 1.6 years; P=.001) and were published more rapidly after submission (median, 0.8 vs 1.1 years; P=.04).\n Among randomized efficacy trials, there is a time lag in the publication of negative findings that occurs mostly after the completion of the trial follow-up.", "The primary aim of the present study was to identify possible occurrence of selective reporting of the results of clinical trials to the Finnish National Agency for Medicines. Selective reporting may lead to poorly informed action or inaction by regulatory authorities.\n In 1987, 274 clinical drug trials were notified to the Finnish National Agency for Medicines. By December 1993, final reports had been received from 68 of these trials and statements that the trial had been suspended from 24 trials. The sponsors of the non-reported trials were requested to report the outcome. The outcomes, if any, of all reported and non-reported trials were classified as positive, inconclusive or negative.\n The total number of trials with positive, inconclusive or negative outcome were 111, 33 and 44, respectively; the outcomes of 86 trials could not be assessed. Final reports were received from 42/111 (38%) trials with positive, 6/33 (18%) with inconclusive and 9/44 (20%) with negative outcomes.\n Substantial evidence of selective reporting was detected, since trials with positive outcome resulted more often in submission of final report to regulatory authority than those with inconclusive or negative outcomes.", "To determine the extent to which publication is influenced by study outcome.\n A cohort of studies submitted to a hospital ethics committee over 10 years were examined retrospectively by reviewing the protocols and by questionnaire. The primary method of analysis was Cox's proportional hazards model.\n University hospital, Sydney, Australia.\n 748 eligible studies submitted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988.\n Time to publication.\n Response to the questionnaire was received for 520 (70%) of the eligible studies. Of the 218 studies analysed with tests of significance, those with positive results (P < 0.05) were much more likely to be published than those with negative results (P > or = 0.10) (hazard ratio 2.32 (95% confidence interval 1.47 to 3.66), P = 0.0003), with a significantly shorter time to publication (median 4.8 v 8.0 years). This finding was even stronger for the group of 130 clinical trials (hazard ratio 3.13 (1.76 to 5.58). P = 0.0001), with median times to publication of 4.7 and 8.0 years respectively. These results were not materially changed after adjusting for other significant predictors of publication. Studies with indefinite conclusions (0.05 < or = P < 0.10) tended to have an even lower publication rate and longer time to publication than studies with negative results (hazard ratio 0.39 (0.13 to 1.12), P = 0.08). For the 103 studies in which outcome was rated qualitatively, there was no clear cut evidence of publication bias, although the number of studies in this group was not large.\n This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor. The study results support the need for prospective registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking systematic reviews.", "Publication bias is widely appreciated, but considerable time and effort are needed to locate and obtain data from unpublished randomized controlled trials (RCTs), those published in non-English language journals or those reported in the gray literature; for this publication, we will call this collection of trials the \"gray+literature.\" However, excluding such trials from systematic reviews could introduce bias and give rise to misleading conclusions.\n We aimed to explore and quantify the impact of inclusion of gray+ literature on the results of all completed individual patient data (IPD) reviews coordinated by our group (13 meta-analyses). For each IPD review, results were calculated for RCTs fully published in English language journals and RCTs fully published in English language journals and the gray+literature.\n The IPD meta-analyses based only on RCTs that were fully published in English language journals tended to give more favorable results than those that included RCTs from the gray+literature. Although in most cases the addition of gray+data gave less encouraging results, moving the estimated treatment effect toward a null result, the direction of effect was not always predictable.\n We recommend that all systematic reviews should at least attempt to identify trials reported in the gray+literature and, where possible, obtain data from them.", "Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions.\n To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication.\n Survey of 510 abstracts from large (sample size, > or =200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (P< or =.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication.\n Publication rate at 5 years; time from presentation to full publication.\n Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P =.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P =.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources.\n A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Nonpublication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards.", "Free papers presented to the Annual Scientific Congress (ASC) of the Royal Australasian College of Surgeons (RACS) were reviewed for the years 1994, 1995 and 1996. Reports were examined for evidence of publication bias.\n Suitable free papers were identified from the proceedings of the meetings and authors were contacted to obtain information about the research reported and any publications resulting from it.\n Responses were obtained from 302 of 576 presentations considered suitable. A total of 55% of responding authors reported publication of their paper. Basic science papers were most likely to be published. There was a significant bias in favour of publication of positive results (98 of 139 positive vs 76 of 159 inconclusive or negative reports; P < 0.01). Retrospective data were as likely to be published as prospective (51% and 57%, respectively). Reports describing studies of high-level evidence were more likely to be published in journals with a high impact factor.\n The ASC is a comprehensive meeting that attracts a wide range of free papers from most sections of the RACS. There appears to be no evidence of bias in selection of papers for inclusion in the meeting but there is bias in the subsequent publication, which favours positive reports.", "Studies with positive results are more likely to be published in biomedical journals than are studies with negative results. However, many studies submitted for consideration at scientific meetings are never published in full; bias in this setting is poorly studied.\n To identify features associated with the fate of research abstracts submitted to a scientific meeting.\n Prospective observational cohort, with 5-year follow-up of all research submitted for consideration to the major annual 1991 US research meeting in the specialty of emergency medicine.\n All research abstracts submitted for consideration at the meeting for possible presentation.\n Characteristics associated with acceptance for presentation at the meeting and subsequent publication as a full manuscript.\n A total of 492 research abstracts were submitted from programs in emergency medicine and other specialties affiliated with 103 US medical schools. A total of 179 (36%) were accepted for presentation and 214 (43%) were published in 44 journals. Of the 179 abstracts accepted for presentation, 111 studies were published. Scientific quality of abstracts or prestige of the journal in which the study was eventually published did not predict either of these outcomes. The best predictors (by logistic regression) of meeting acceptance were a subjective \"originality\" factor (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.13-3.89) and positive results (OR, 1.99; 95% CI, 1.07-3.84), and, for publication, meeting acceptance (OR, 2.49; 95% CI, 1.49-4.35) and large sample size (OR, 2.26; 95% CI, 1.23-4.31). Forty-nine percent (241) of abstracts did not report on blinding, and 24% (118) did not report on randomization. Acceptance and publication were both more likely for positive outcomes (P=.03). Funnel plots showed the classic distribution of positive-outcome (\"publication\") bias at each of the submission, acceptance, and publication phases. Meeting acceptance predicted publication with a sensitivity of only 51%, specificity of 71%, positive predictive value of 57%, and negative predictive value of 66%.\n Positive-outcome bias was evident when studies were submitted for consideration and was amplified in the selection of abstracts for both presentation and publication, neither of which was strongly related to study design or quality.", "Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly." ]

[ "2205286", "8179545", "9511686", "6805497", "9662321", "1547164", "7100360", "6726592", "17158417" ]

[ "The implications of introducing the symphyseal-fundal height-measurement. A prospective randomized controlled trial.", "A randomized controlled trial in a hospital population of ultrasound measurement screening for the small for dates baby.", "Positive effects of an antenatal group teaching session on postnatal nipple pain, nipple trauma and breast feeding rates.", "Predictive value of ultrasound measurement in early pregnancy: a randomized controlled trial.", "Comparison of the modified biophysical profile to a \"new\" biophysical profile incorporating the middle cerebral artery to umbilical artery velocity flow systolic/diastolic ratio.", "Does admission to hospital for bed rest prevent disease progression or improve fetal outcome in pregnancy complicated by non-proteinuric hypertension?", "Health beliefs and health care behaviour in pregnancy.", "Is routine hospitalization needed in antenatal care of twin pregnancy?", "Posthospital discharge feeding for preterm infants: effects of standard compared with enriched milk formula on growth, bone mass, and body composition." ]

[ "A total of 1639 women attending the antenatal clinic of Gentofte University Hospital, Copenhagen, during 1986-1987 was randomized into a symphyseal fundal (SF)-group and a control group. The women in the SF-group had their fundal height measured from the 29th week until delivery. The measurements were used along with the other usual screening procedures. The SF-measurements were not found helpful in the prediction of small-for-gestational-age infants and no significant differences were found between the two groups regarding the number of interventions, additional diagnostic procedures, or the condition of the newborns.", "Poor fetal growth is an important cause of perinatal mortality and morbidity. Based on the hypothesis that early diagnosis of fetal growth problems leads to more appropriate management and therefore, improved outcome, a randomized controlled trial of ultrasound measurement was performed on 1,528 women booked through a hospital antenatal clinic. This compared a number of perinatal outcomes between the group who had a routine 2-stage examination (early dating and 34-week scan) and a group who had only a dating scan and then additional scans as generated by their clinical situations. No significant differences could be found between the groups when these perinatal outcomes were considered. These results mirror previously published randomized controlled trials. Selection of women for third trimester ultrasound examination for suspected fetal growth problems should be based on careful clinical assessment and should not be routine.", "To assess whether an antenatal teaching session on position and attachment of the baby on the breast had an effect on postnatal nipple pain, nipple trauma and breast feeding duration. The study was planned as a pilot study to allow an adequate sample size to be calculated for a larger study.\n An observer blind experimental design was used. Women were randomly assigned to either the experimental group teaching session or the control group.\n One public hospital in Western Australia.\n 70 primiparae who intended to breast feed their baby were recruited from the antenatal clinic of the study hospital at 36 weeks' gestation.\n Antenatal group sessions on position and attachment of the baby on the breast were conducted by a lactation consultant.\n During the first four postnatal days, position and attachment was measured by LATCH (Latch on, Audible swallow, Type of nipple, Comfort and Help) (Jensen et al 1994), nipple pain was measured by the Visual Analogue Scale (VAS) and nipple trauma was measured by the Nipple Trauma Index (NTI). The analysis of variance (ANOVA) results indicated that the women in the experimental group were better able to attach the baby on the breast and had significantly less nipple pain and trauma than the control group. At six weeks postnatally, 31 of the 35 women in the experimental group were breast feeding compared to 10 of the 35 in the control group.\n These initial findings suggest that midwives can make the best use of decreasing resources by using practical 'hands on' antenatal group teaching as an effective strategy to increase breast feeding rates.", "Early fetal biparietal diameter (BPD) measurements were obtained with ultrasound in 1062 women attending for antenatal care; a random half had the results withheld from the obstetricians. Of the 1026 women who were sure of the dates of their last normal menstrual period, 829 (81%) were found to have appropriate biparietal diameter measurements, in 3% the pregnancy was more than 2 weeks further advanced and in 14% more than 2 weeks less than calculated. In 30% of the women whose results were intended to be withheld, the code had to be broken because of clinical concern. There were no differences in fetal outcome (birthweight centile, Apgar score at 1 min and perinatal mortality) in the women whose BPD results were known compared with those whose results were withheld from the obstetrician. But a significantly larger number of labours were induced for suspected growth retardation when the gestational age was known.", "The objective of this study was to determine whether the addition of the middle cerebral to umbilical artery systolic/diastolic velocity waveform ratio to the modified biophysical profile would improve perinatal outcome in patients at high risk.\n A prospective, randomized outcome study of patients referred to the perinatal laboratory for antenatal surveillance was undertaken. Six hundred sixty-five patients were randomized to two antenatal surveillance protocols: group 1, modified biophysical profile; and group 2, modified biophysical profile plus evaluation of the middle cerebral artery to umbilical artery systolic/diastolic ratio. Patients were followed up serially and neonatal outcome data including gestational age at delivery, birth weight, incidence of cesarean section delivery for fetal distress, admission to the neonatal intensive care unit, days in the neonatal intensive care unit, and the presence of significant neonatal morbidity were tabulated.\n The total population showed no statistical difference in outcome parameters between groups 1 and 2. However, a subgroup of patients evaluated for suspected uteroplacental insufficiency did show a significant reduction in caesarean section for fetal distress in group 2 patients.\n In a subgroup of patients at risk for uteroplacental insufficiency, the addition of the middle cerebral/umbilical artery ratio to an antenatal surveillance protocol should be expected to improve perinatal outcome.", "To test whether a policy of admission to hospital for rest is of value in the management of women with non-proteinuric hypertension during pregnancy.\n A randomized controlled trial.\n Harare Maternity Hospital, Zimbabwe.\n 218 (28 first pregnancies) women with non-proteinuric hypertension and a singleton pregnancy at between 28 and 38 weeks gestation allocated to rest in hospital or routine outpatient care.\n Admission to hospital for rest. Encouraged to rest in bed although voluntary ambulation around the ward was allowed. The women in the control group were encouraged to continue normal activity at home, to check urine each day for proteinuria. All the women were reviewed weekly.\n Disease progression was assessed by the development of severe hypertension (greater than or equal to 160/110 mmHg), development of proteinuria, need for induction of labour and number of infants born preterm (less than 37 weeks). Fetal outcome was assessed by birthweight, number of infants small-for-gestational age (SGA), and the number of infants requiring admission to the neonatal unit and their length of stay.\n The hospital rest group had a decreased risk of developing severe hypertension (blood pressure greater than or equal to 160/110 mmHg [odds ratio 0.47, 95% CI 0.26-0.83]). No differences were found in fetal growth or neonatal morbidity. The mean antenatal stay in hospital was 22.2 (SD 16.5), and 6.5 (SD 7.9) days in the rest and control groups, respectively.\n Hospital admission for bed rest decreased the risk of developing severe hypertension but no improvement in fetal growth or neonatal morbidity was observed. Fetal monitoring at home and continued outpatient antenatal care provided a safe, alternative policy to hospital admission.", "Primiparae were randomly assigned to two conditions of routine ultrasound examination at their first antenatal clinic visit: (a) high feedback ultrasound where the monitor screen was visible and the patient was shown the foetal size, shape and movement (N = 67); (b) low feedback ultrasound where the screen was not seen and specific verbal feedback was denied (N = 62). Women were interviewed at 16 weeks gestation. Those receiving high feedback were more likely to report that they had acted on health advice given at the first antenatal visit to reduce their smoking and drinking.", "A prospective study was carried out to evaluate the significance and efficacy of routine hospital bed rest in prevention of premature birth and pregnancy complications compared to specialized antenatal care at the outpatient clinic of 73 twin pregnancies. The twin pregnancies were screened in health centers by means of symphysis-fundus measurement, and the diagnosis was confirmed by ultrasound examination at the outpatient clinic. On the average the ultrasonic diagnosis was performed during the 23rd gestational week; at this visit the women were divided into two groups with similar follow-up to the end of the 29th gestational week. At this stage one of the groups was hospitalized unless there had been indications for earlier admission. In the hospital group, the mean for gestational week at delivery was 36.7 (+/- 2.4) and in the outpatient group 37.4 (+/- 1.8) respectively (N.S.). There was no difference in the rate of pregnancy complications between the groups too. No statistical differences in the perinatal mortality (7.1% and 1.1% respectively) or birthweights of the newborns were found, either. Present results do not support the idea of using routine hospital bed rest. It could not be proved to have positive effects on the gestational age, birth weight and perinatal mortality of the newborns, nor to the pregnancy complications. In our opinion early diagnosis of twin pregnancy is of decisive importance and specialized ambulatory follow-up could be employed instead of routine bed rest in antenatal care of twin pregnancy.", "Despite the theoretical benefits of nutrient-enriched formula given to preterm infants after hospital discharge, its role in reversing growth deficits after hospital discharge remains poorly defined.\n The aim was to determine the effect of different formulas on the growth, bone mass, and body composition of preterm infants after hospital discharge.\n This was a randomized, double blind comparison of a nutrient-enriched formula (EF) and a formula for term infants (TF) given for 1 y after hospital discharge. Compared with the TF, the EF had a higher energy density and higher contents of protein, calcium, and phosphorus (by 10%, 21%, 44%, and 11%, respectively) and higher contents of almost all other nutrients (by >or=10%).\n Birth weights of the infants were 630-1620 g (median: 1250 g) and gestational ages were 24-34 wk (median: 29 wk). TF resulted in significantly greater weight, length, head circumference measurements, and their respective z scores on the basis of age- and sex-specific norms. At the end of the study, the mean z scores for the corrected age of infants in the TF group were -0.37 for weight, 0.001 for length, and 0.50 for head circumference. The TF group also had significantly greater dual-energy X-ray absorptiometry measured bone and lean and fat mass than did the EF group (P < 0.05 for all comparisons).\n The use of EF for preterm infants after hospital discharge shows no advantage over TF in growth, bone mineralization, and body composition. More studies are needed to determine the optimal postdischarge nutrition support for preterm infants." ]

[ "11477970", "8571154", "8356485", "12973646", "10155878", "15686063", "15746218", "1958910", "12017833" ]

[ "Effect of removing user fees on attendance for curative and preventive primary health care services in rural South Africa.", "Impact of user charges on vulnerable groups: the case of Kibwezi in rural Kenya.", "User fees plus quality equals improved access to health care: results of a field experiment in Cameroon.", "Fees-for-services, cost recovery, and equity in a district of Burkina Faso operating the Bamako Initiative.", "The fall and rise of cost sharing in Kenya: the impact of phased implementation.", "The impact of user fee exemption on service utilization and treatment seeking behaviour: the case of malaria in Sudan.", "Abolition of cost-sharing is pro-poor: evidence from Uganda.", "Online access to MEDLINE in clinical settings: impact of user fees.", "User charges and utilisation of obstetric services in the National Capital District, Papua New Guinea." ]

[ "User fees are used to recover costs and discourage unnecessary attendance at primary care clinics in many developing countries. In South Africa, user fees for children aged under 6 years and pregnant women were removed in 1994, and in 1997 all user fees at all primary health care clinics were abolished. The intention of these policy changes was to improve access to health services for previously disadvantaged communities. We investigated the impact of these changes on clinic attendance patterns in Hlabisa health district. Average quarterly new registrations and total attendances for preventive services (antenatal care, immunization, growth monitoring) and curative services (treatment of ailments) at a mobile primary health care unit were studied from 1992 to 1998. Regression analysis was undertaken to assess whether trends were statistically significant. There was a sustained increase in new registrations (P = 0.0001) and total attendances (P = 0.0001) for curative services, and a fall in new registrations (P = 0.01) and total attendances for immunization and growth monitoring (P = 0.0002) over the study period. The upturn in demand for curative services started at the time of the first policy change. The decreases in antenatal registrations (P = 0.07) and attendances (P = 0.09) were not statistically significant. The number of new registrations for immunization and growth monitoring increased following the first policy change but declined thereafter. We found no evidence that the second policy change influenced underlying trends. The removal of user fees improved access to curative services but this may have happened at the expense of some preventive services. Governments should remain vigilant about the effects of new health policies in order to ensure that objectives are being met.", "The Government of Kenya introduced user fees for inpatient and curative outpatient care at its hospitals and health centres in December 1989. Children under five years old and those judged by the health staff to be indigent were among the groups exempted from fees. In September 1990, outpatient registration fees were removed, but other fees were retained. This paper describes the effects of these policy changes on the use of health services in Kibwezi division, a poor rural area. It focuses particularly on the impact of the fees on access to care by children and the poor. The assessment is based on attendance data from government health facilities and on a longitudinal household survey of health care utilization, which covered the nine months during which all fees were charged and two months following the removal of the registration fees. Attendance at government fee-charging health facilities for both outpatient and inpatient care was lower during the period when full fees were charged than during the same months of the previous year. Outpatient attendances rose again when the registration fees were lifted. The study households reported lower levels of utilization of public hospitals and health centres when full fees were in force than during the period after the registration fees were lifted. The pattern of utilization by young children, who were exempted from fees, mirrored that of the rest of the population, suggesting that they were not fully protected from the adverse effects of fees. The poorest households made much less use of the fee-charging government facilities than the better-off households.(ABSTRACT TRUNCATED AT 250 WORDS)", "Since the Bamako Initiative was launched in 1988, many African countries have embarked on comprehensive primary health care programs relying, at least partially, on revenues generated through user fees to revitalize health care delivery systems. Although these programs contain two critical components, user fees and improved quality, policy debates have tended to focus on the former and disregarded the latter. The purpose of this study is to provide a net assessment of these two components by testing how user fees and improved quality affect health facility utilization among the overall population and specifically among the poorest people. A \"pretest-posttest controlled\" experiment was conducted in five public health facilities in the Adamaoua province of Cameroon. Three health centers which were to introduce a user fee and quality improvement (i.e. reliable drug supply) policy were selected as \"treatment\" centers and two comparable facilities not yet phased into this policy were selected as \"controls\". Two rounds of household surveys were conducted (each to 800 households in 25 villages surrounding the five study sites) to measure the percentage of ill people seeking care at the health center before and after the implementation of the policy. The experiment was tightly controlled by conducting monthly observations at each study site. Results indicate that the probability of using the health center increased significantly for people in the \"treatment\" areas compared to those in the \"control\" areas. Travel and time costs involved in seeking alternative sources of care are high; when good quality drugs became available at the local health center, the fee charged for care and treatment represented an effective reduction in the price of care and thus utilization rose. Moreover, contrary to previous studies which have found that the poorest quintile is most hurt by user fees, this study found that probability of the poorest quintile seeking care increases at a rate proportionately greater than the rest of the population. Since the poor are most responsive to price changes, they appear to be benefitting from local availability of drugs more than others.", "To gauge the effects of operating the Bamako Initiative in Kongoussi district, Burkina Faso.\n Qualitative and quasi-experimental quantitative methodologies were used.\n Following the introduction of fees-for-services in July 1997, the number of consultations for curative care fell over a period of three years by an average of 15.4% at \"case\" health centres but increased by 30.5% at \"control\" health centres. Moreover, although the operational results for essential drugs depots were not known, expenditure increased on average 2.7 times more than income and did not keep pace with the decline in the utilization of services. Persons in charge of the management committees had difficulties in releasing funds to ensure access to care for the poor.\n The introduction of fees-for-services had an adverse effect on service utilization. The study district is in a position to bear the financial cost of taking care of the poor and the community is able to identify such people. Incentives must be introduced by the state and be swiftly applied so that the communities agree to a more equitable system and thereby allow access to care for those excluded from services because they are unable to pay.", "The combined effects of increasing demand for health services and declining real public resources have recently led many governments in the developing world to explore various health financing alternatives. Faced with a significant decline during the 1980s in its real per capita expenditures, the Kenya Ministry of Health (MOH) introduced a new cost sharing programme in December 1989. The programme was part of a comprehensive health financing strategy which also included social insurance, efficiency measures, and private sector development. Early implementation problems led to the suspension in September 1990 of the outpatient registration fee, the major revenue source at the time. In 1991, the Ministry initiated a programme of management improvement and gradual re-introduction of an outpatient fee, but this time as a treatment fee. The new programme was carried out in phases, beginning at the national and provincial levels and proceeding to the local level. The impact of these changes was assessed with national revenue collection reports, quality of care surveys in 6 purposively selected indicator districts, and time series analysis of monthly utilization in these same districts. In contrast to the significant fall in revenue experienced over the period of the initial programme, the later management improvements and fee adjustments resulted in steady increases in revenue. As a percentage of total non-staff expenditures, fiscal year 1993-1994 revenue is estimated to have been 37% at provincial general hospitals, 20% at smaller hospitals, and 21% at health centres. Roughly one third of total revenue is derived from national insurance claims. Quality of care measures, though in some respects improved with cost sharing, were in general somewhat mixed and inconsistent. The 1989 outpatient registration fee led to an average reduction in utilization of 27% at provincial hospitals, 45% at district hospitals, and 33% at health centres. In contrast, phased introduction of the outpatient treatment fee beginning in 1992, combined with somewhat broader exemptions, was associated with much smaller decreases in outpatient utilization. It is suggested that implementing user fees in phases by level of health facility is important to gain patient acceptance, to develop the requisite management systems, and to orient ministry staff to the new systems.", "This experimental study was undertaken to assess the effect of different levels of exemption, 25%, 50% and 75%, from health centre user fees on health service utilization and treatment seeking behaviour for malaria by a high risk group of pregnant women and children under 5 years. These are groups in need of special medical attention to prevent progression of the disease into complicated or severe malaria. Sinnar State, one of Sudan's highly endemic malaria regions, was selected to be the experimental area. Exemptions were introduced for one year in six health centres. Two centres for each exemption level, and a further two health centres without exemptions were studied. At the beginning and the end of the trial year, households surveys were conducted in the catchment areas of the health centres, and focus group discussions with pregnant women and mothers of children under 5 years were conducted. Routine data were reviewed for malaria cases in the health centres and six studies on malaria cases were done upon exit from the health centres. In-depth interviews with health staff of the health centres were conducted. Exemption from user fees increased health services utilization, improved treatment-seeking behaviour and promoted early diagnosis. The changes during the experimental year were the largest in the centres with the largest exemption. Therefore, policy changes towards exemptions are necessary to facilitate early diagnosis and treatment of malaria.", "To document the effects of the abolition of user fees on utilization of health services in Uganda with emphasis on poor and vulnerable groups.\n A longitudinal study using quantitative and qualitative methods was carried out in 106 health facilities across the country. Health records were reviewed to determine trends in overall utilization patterns and use among vulnerable groups. A modification of wealth ranking as defined by the Uganda Poverty Participatory Assessment Project was used to categorize households by socio-economic status in order to compare utilization by the poor against that of other socio-economic groups.\n There was a marked increase in utilization in all population groups that was fluctuating in nature. The increase in utilization varied from 26% in public referral facilities in 2001, rising to 55% in 2002 compared with 2000. The corresponding figures for the lower level facilities were 44% and 77%, respectively. Increase in utilization among the poor was more than for other socio-economic categories. Women utilized health services more than men both before and after cost-sharing. Higher increases in utilization were noted among the over-five age group compared with the under-fives. There were no increases in utilization for preventive and inpatient services. With respect to quality of care, there were fewer drug stock-outs in 2002 compared with 2000 and 2001. There was no deterioration of other indicators such as cleanliness, compound maintenance and staff availability reported.\n The study suggests that there is a financial barrier created by cost-sharing that decreases access to services, especially among the poor in Uganda. However, further studies are needed to clarify issues of utilization by age and gender.", "The effect of introducing user fees on the frequency and quality of MEDLINE searching with GRATEFUL MED by physicians in clinical settings was tested. After training and free use (prior study), consenting participants were randomly allocated to pay searching costs (pay group) or continue without fees (no pay group). Fifty-nine physicians participated. Among the prior study's frequent searchers, the pay group searched at less than one third of the rate of those assigned to no pay. For less frequent searchers in the prior study, only 48% of those assigned to pay did any searches, compared with 85% for the no pay group (P = 0.006), and for those who did search, their frequency was almost half. However, there was no significant difference in the quality of searches; both groups demonstrated about equivalent recall (P = 0.77), but significantly lower precision (P = 0.03) than for the librarian's independent searches. Similarly, there was no difference in the proportion of searches affecting clinical decisions for the two groups. Thus, imposing user charges for online searching in clinical settings after a period of free use adversely affects searching quantity, but not quality. MEDLINE providers should consider whether user fees will undermine its benefits.", "This cross-sectional study examined user charges on the utilization of obstetric services in the 4 urban clinics and antenatal and postnatal wards of the Port Moresby General Hospital (PMGH) in the National Capital District, Papua New Guinea. Analysis of previous records showed attendance to antenatal clinics on first visits declined by 30% soon after the introduction of use charges. However, the frequency of attendances increased and stabilized 12 months after the introduction of the user fees. The mean age for the 482 mothers interviewed was 25 years (range = 15-46 years, SD = 5.3). Over 50% of mothers were between 15-24 years of age and 47% over 24 years. 98.6% were married and a small proportion were single and divorcees (1.4%). Over 85% of mothers had some formal education while 15% without. The frequency of hospital deliveries did not change despite increased in user charges in the PMGH delivery and postnatal care services. Twenty four percent of mothers interviewed indicated they were unable to pay user fees. Mothers unable to pay the user charges were those without income or whose spouses were without regular income. In 23.2% of mothers with some income, majority indicated ability to pay the user fees. There was a minority group of mothers without income but relied heavily on their spouses income to meet the user fees. Mothers living in households with some income were twice more likely (OR = 2.18, 95% CI 1.24-3.83, p = 0.002) to have the ability to pay user fees than those without. Two other significant indicators associated with mother's ability to pay user fees were employment and knowledge of existence of the user charges. Over 79% of mothers indicated willingness to pay user charge fees. Mothers with income were nearly three times more likely (OR = 2.77, 95% CI 1.36-5.78, p = 0.002) willing to pay user charge fees than those without income. Other indicators that showed significant association with willingness to pay user charge fees were employment, income and knowledge of user charges. Although small proportion of mothers were unable to meet the user charges, results in this study showed majority of mothers were able and willing to pay user charges if they had prior information to the charges and supported by some form of income. The results of the study suggests the typical support practised by the society where the spouse and relatives assist with health care especially with maternal health is encouraging. However, the scope of this study cannot be used to generalise the trend in PNG because the scenerio in the rural areas will vary from urban." ]

[ "14872039", "10487186", "10486394", "10691121", "2498073", "55587", "10441604", "2360466", "1402964" ]

[ "Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study.", "Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents.", "Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects.", "A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy.", "Controlled trial of lamotrigine (Lamictal) for refractory partial seizures.", "Anticonvulsants and parental epilepsy in the development of birth defects.", "Phenobarbital compared with phenytoin for the treatment of neonatal seizures.", "Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours.", "Do prophylactic anticonvulsant drugs alter the pattern of seizures after craniotomy?" ]

[ "The authors conducted a randomized trial of second-line anticonvulsant treatments for neonates. The response to treatment was assessed using continuous video-EEG because the clinical diagnosis of seizure in neonates is known to be unreliable. Of 27 neonates with EEG-confirmed seizures, 5 were excluded because of protocol violations, and 11 responded to phenobarbitone in a dose of 40 mg/kg as first line. Three of five neonates treated with lignocaine responded. Six neonates were treated with benzodiazepines as second line: None responded, and their neurodevelopmental outcome was poor.", "Antiepileptic drugs (AEDs) are potential teratogenic agents. The purpose of this study was to examine the long-term effects of intrauterine AED exposure on neurologic and psychological functioning.\n Of a prospective study, \"Epilepsy, pregnancy, and child development,\" children could be retraced at school age and adolescence. Sixty-seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects.\n Type of maternal epilepsy and type and kind of AED therapy, but not maternal seizures during pregnancy correlated with an increase in abnormal EEG patterns. Minor neurologic dysfunction was diagnosed, with increased frequency from the control to the risk/no drug or monotherapy to the polytherapy group. The compromised intelligence score of the polytherapy group was primarily due to those children who had been exposed to primidone (PRM). Level of IQ was negatively associated with PRM dosage.\n Maternal epilepsy and AED therapy during pregnancy appear to have long-term effects on the offspring well into adolescence, as evinced in EEG patterns, minor neurologic dysfunction, and intellectual performance. Severity of effects increased from control group to epilepsy/no-drug group to monotherapy group and was most marked in the polytherapy group. These group differences are assumed to reflect differential neural vulnerability to social and family factors.", "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.", "To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy.\n One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated.\n Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups.\n Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population.", "The antiepileptic effect of lamotrigine (LTG) was assessed in a double-blind, placebo-controlled crossover trial in 24 adult patients with refractory partial seizures. LTG or placebo was added to existing antiepileptic drugs (AEDs). The dose of LTG varied from 75 to 400 mg daily. Three patients did not complete the trial. One was withdrawn from the trial with ataxia, tiredness, dyspnea, and diplopia while receiving LTG and died 18 days later of invasive carcinoma involving the liver. A second patient was withdrawn during baseline for contravening admission criteria, and a third received LTG in error during both treatment periods. Twenty-one patients (12 men and 9 women) completed the trial. An analysis of seizure counts in the 12-week treatment period with LTG showed a statistically significant reduction in seizures as compared with placebo for total seizures (p less than 0.002), partial seizures (p less than 0.002), and secondarily generalized seizures (p less than 0.05). The analysis of total seizure days showed a significant reduction during LTG treatment (p less than 0.002). There were no statistically significant changes in plasma concentrations of phenytoin (PHT), carbamazepine (CBZ), primidone (PRM), or phenobarbital (PB) between the two treatment periods. The most common adverse events reported during the trial were diplopia, drowsiness, tiredness, ataxia, and headache, but although these were more frequent during LTG treatment, the differences from placebo were not statistically significant. No hematological or biochemical changes were noted.", "The results of two studies, one in Finland and one in the U.S.A., raise the possibility that fetal damage previously attributed to phenytoin and other anticonvulsant drugs, principally phenobarbitone, may be due to epilepsy itself. In the U.S.A., drug-exposure information was collected before delivery in a cohort of 50 282 mother/child pairs. The total malformation rate in 305 children born to epileptic mothers was 10.5%, as against 6.4% in the remainder (p less than 0.01); corresponding rates for major malformations were 6.6% and 2.7%. When the fathers had epilepsy, the malformation-rates in their children were intermediate. The rates did not vary significantly according to maternal anticonvulsants therapy. Mental and motor scores as 8 months of age, and intelligence quotient scores at 4 years were lower in children of epileptic mothers, but not in children of epileptic fathers. The scores showed only random variation according to maternal anticonvulsant therapy. In Finland, 2784 children with craniofacial anomalies were compared with an equal number of normal children; 8 and 2 mothers, respectively, received anticonvulsants, while pregnant, for epilepsy. In that study, the separate effects of the disease and its treatmet could not be evaluated. Both studies did not find evidence of fetal damage when phenobarbitone was taken for indications other than epilepsy.", "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.", "One hundred and twenty-eight adult patients presenting with and operated on for supratentorial neoplasms were studied. Sixty-five had preoperative seizures and were treated with antiepileptic drugs (AEDs). Among the 63 patients without preoperative epileptic fits, 41 were given AEDs (either phenobarbital or phenytoin) as prophylactic treatment and 22 were not treated. The preoperative epilepsy course was considered with respect to tumour site and histological type. Early and late postoperative seizure occurrence was considered in the different groups of patients. The results suggest the usefulness of a short term preventive treatment with AEDs after surgery in patients without preoperative seizures. In patients with preoperative epilepsy, AEDs should be continued after surgery. However long-term AEDs treatment should not be recommended in patients without preoperative epilepsy. In fact, no significant difference in late seizure occurrence was found between preventively treated and untreated patients.", "A total of 276 patients with a high risk of developing postoperative seizures were randomised to treatment with carbamazepine or phenytoin for six or 24 months, or to no treatment. No significant differences were found (though the confidence limits were fairly wide) between the regimes in respect of the incidence of seizures or death. In a substantial proportion of the patients postoperative epilepsy remained a continuing disability. A high incidence of drug-related side effects was found in the treatment groups. Prophylactic anticonvulsants cannot therefore be recommended routinely following supratentorial craniotomy." ]

[ "17568029", "20659937", "11759644", "19504425", "18057479", "8970221", "3276336", "331941", "16395687" ]

[ "A multicenter, randomized trial of prophylactic fluconazole in preterm neonates.", "Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants.", "Fluconazole prophylaxis against fungal colonization and infection in preterm infants.", "Comparison of fluconazole and nystatin oral suspensions for prophylaxis of systemic fungal infection in very low birthweight infants.", "Fluconazole prophylaxis against fungal colonization and invasive fungal infection in very low birth weight infants.", "Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial.", "Prophylactic oral nystatin and fungal infections in very-low-birthweight infants.", "Staphylococcal and streptococcal colonization of the newborn infant: effect of antiseptic cord care.", "Prevention and monitoring of invasive fungal infections in pediatric patients with cancer and hematologic disorders." ]

[ "Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates.\n During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing.\n Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P<0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant candida species was observed, but the study did not have substantial power to detect such an effect.\n Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).\n Copyright 2007 Massachusetts Medical Society.", "Invasive fungal infections are a major cause of morbidity and mortality in preterm infants. The authors conducted the first prospective, randomised controlled trial of nystatin compared with fluconazole for the prevention of fungal colonisation and invasive fungal infection in very low birth weight (VLBW) neonates.\n During a 12-month period, all VLBW neonates were assigned randomly to receive nystatin (1 ml suspension, 100 000 U/ml, every 8 h), fluconazole (3 mg/kg body weight, every third day) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). The authors performed weekly surveillance cultures and systemic fungal susceptibility testing.\n During the study period, 278 infants (fluconazole group, n=93; nystatin group, n=94; control group, n=91) weighing <1500 g at birth were admitted. There were no differences in birth weight, gestation, gender or risk factors for fungal infection among the groups. Fungal colonisation occurred in 11.7% of the nystatin group and 10.8% of the fluconazole group, as compared with 42.9% of the control group. The incidence of invasive fungal infection was 4.3% in the nystatin group and 3.2% in the fluconazole group, as compared with 16.5% in the control group. There were no differences in fungal colonisation and invasive fungal infection between the nystatin and fluconazole groups.\n Prophylactic nystatin and fluconazole reduce the incidence of colonisation and invasive fungal infection in VLBW neonates. The authors believe that nystatin is an alternative to fluconazole, because nystatin is safe, inexpensive, well tolerated and effective.", "Invasive fungal infection is associated with substantial morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing fungal colonization and invasive infection in extremely-low-birth-weight infants.\n We conducted a prospective, randomized, double-blind clinical trial over a 30-month period in 100 preterm infants with birth weights of less than 1000 g. The infants were randomly assigned during the first five days of life to receive either intravenous fluconazole or placebo for six weeks. We obtained weekly surveillance cultures from all patients.\n The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, and base-line risk factors for fungal infection. During the six-week treatment period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; difference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.002). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008). The sensitivities of the fungal isolates to fluconazole did not change during the study, and no adverse effects of the fluconazole therapy were documented.\n Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g.", "We compared the efficacy and safety of fluconazole and nystatin oral suspensions for the prevention of systemic fungal infection (SFI) in very low birthweight infants. A prospective, randomized clinical trial was conducted over a 15-month period, from May 1997 through September 1998, in 80 preterm infants with birthweights <1500 g. The infants were randomly assigned to receive oral fluconazole or nystatin, beginning within the first week of life. Prophylaxis was continued until full oral feedings were attained. Blood and urine cultures were obtained at enrollment and then weekly thereafter. Thirty-eight infants were randomly assigned to receive oral fluconazole (group I), and 42 infants were assigned to receive nystatin (group II). Birthweight, gestational age, and risk factors for fungal colonization and SFI at the time of randomization and during the hospital course were similar in both groups. SFI developed in two infants (5.3%) in group I and six infants (14.3%) in group II. The difference between these two rates was not statistically significant (relative risk, 0.37; 95% confidence interval, 0.08 to 1.72). There were no deaths in group I and six deaths in group II (P = 0.03). Two infants died of neonatal sepsis, and four deaths were related to necrotizing enterocolitis and/or spontaneous intestinal perforation. No deaths were due to SFI. Enrollment was halted before completion and the study did not attain adequate power to detect a hypothesized drop in SFI rate from 15 to 5%. Although the results cannot justify any conclusion about the relative efficacy of fluconazole versus nystatin in prevention of SFI, the significantly higher mortality rate in the nystatin group raises questions about the relative safety of this medication.\n Thieme Medical Publishers.", "Fungal infections are common cause of morbidity and mortality in very low birth weight Infants\n To evaluate the efficacy of prophylactic Fluconazole in preventing fungal colonization and invasive fungal infection in VLBW infants.\n Prospective, randomized, double blind placebo controlled clinical trial.\n Tertiary level Neonatal intensive care unit.\n 120 preterm infants with birth Weight < 1500 g.\n Infants were randomly assigned during first three days to receive either Fluconazole or placebo till 28 days or less if, discharged or died earlier. Weekly surveillance cultures from groin, oropharynx, rectum and blood were collected in all patients. Fungal isolates were typed based on standard microbiologic techniques. Liver enzymes were monitored.\n Baseline risk factors for fungal infection in Fluconazole and Placebo groups were similar. Fungal colonization was seen in 30 infants (50%) in the placebo group and 11 infants (19%) in the Fluconazole group (P <0.001). Fungal colonization at rectum, groin and oropharynx was less in fluconazole groups. Fluconazole group showed significantly lower colonizations with Candida albicans but not with C. glabrata. Invasive infection was seen in 15 (25%) infants in Placebo group and 16 (26.7%) infants in Fluconazole group (P = 0.835). Various non-albicans Candida were responsible for 96.8% cases of invasive fungal infection (Candida glabrata 71%, C. parapsilosis 14.7% and C. tropicalis 9.6%). No significant hepatotoxicity was noticed during Fluconazole therapy.\n Prophylactic fluconazole during the first four weeks of life is effective in reducing fungal colonization but not invasive infection in VLBW infants.", "Fungal septicemia is a devastating disease in the neonate, especially in the low birth weight preterm infant who is especially vulnerable to disseminated fungal sepsis. The objective of this study was to compare the efficacy, safety and overall convenience of fluconazole vs. amphotericin B for the treatment of disseminated fungal sepsis in neonates.\n A prospective, randomized, collaborative study conducted at two South African neonatal units.\n Twenty-four infants with proven fungal septicemia were treated from June, 1992, to June, 1993. Twelve received fluconazole, 11 received amphotericin B and 1 was excluded. Assessment of hepatic, renal and hematologic functions were performed before, during and after treatment. The two groups were comparable at the time of enrollment into the study.\n Infants receiving amphotericin B had significantly higher values of total and direct bilirubin and alkaline phosphatase values at the end of treatment, while the fluconazole group showed a significant increase in the platelet count. The cumulative total numbers of days receiving intravenous therapy for the administration of antifungal drugs were 57 for the fluconazole group and 162 for the amphotericin group; no central lines were needed in the fluconazole group, whereas 3 babies given amphotericin B had central catheters for a cumulative total of 27 days. The case fatality rate was 33% in the fluconazole group and 45% in the amphotericin B group; there was still proof of fungal septicemia at the time of death in 1 patient given amphotericin B and 2 given fluconazole.\n Fluconazole showed fewer side effects than amphotericin B and was more convenient to use.", "Prevention of systemic fungal infection in the very-low-birthweight infant is important since it is associated with a high morbidity and mortality. To determine if oral nystatin administration could prevent fungal colonization and infection, we evaluated 67 preterm infants with birthweights less than 1250 gm. Thirty-three infants received 1 ml (100,000 units/ml) of nystatin inside the mouth every 8 hours until 1 week after extubation. Oropharyngeal, rectal, blood, and urine cultures were obtained on the 1st day of life and weekly. Endotracheal cultures were obtained three times a week from intubated infants. Four (12%) of the 33 nystatin-treated infants had positive cultures, two (6%) developed systemic infection. The control group consisted of 34 infants, 15 (44%) had positive fungal cultures and 11 (32%) developed systemic infection. Fungi isolated were Candida species and Torulopsis glabrata. Colonized infants were dependent on the respirator (P less than 0.001), had indwelling catheters (P less than 0.01), and received antibiotics (P less than 0.05) for a longer period than infants free from fungi and their mortality was significantly higher (P less than 0.05). We conclude that prophylactic administration of oral nystatin reduces fungal colonization and infection in very-low-birthweight infants.", "A randomized controlled study was undertaken to compare the effectiveness of three umbilical cord treatment regimens in controlling neonatal bacterial colonization. The three regimens studied included castile soap, triple dye, and silver sulfadiazine. The triple dye and silver sulfadiazine application inhibited bacterial colonization. Staphylococcal colonization was inhibited by both treatment regimens but most effectively by triple dye. Group B streptococcal colonization was inhibited most effectively by silver sulfadiazine while triple dye application to the umbilicus promoted colonization with this microorganism. Silver sulfadiazine was more effective in controlling colonization with Gram-negative microorganisms.", "The occurrence of invasive fungal infection (IFIs) in a pediatric hematology/oncology unit after renovation of the ventilation system, and initiating routine azole antifungal prophylaxis was monitored. In addition, the value of serial screening for Aspergillus galactomannan (GM) for diagnosing invasive aspergillosis was assessed.\n A total of 98 consecutive high-risk pediatric patients were prospectively surveyed for signs of IFI and weekly monitored for serum GM. The data was not made available to treating physicians.\n Only 2 patients had proven and 27 possible IFI based on the European Organization for Research and Treatment of Cancer/Mycoses Study Group definitions. The incidence of proven IFI was 1/31 (3.2%) in the allogeneic stem cell transplant (SCT) (Aspergillus spp), 0/26 in the autologous SCT, and 1/60 (1.6%) in the induction therapy group (C. krusei). GM was detected at least in one tested sample in 12/98 patients (12.2%), in five patients in two or more sequential samples. In the latter group, IFI was proven in one patient and could not be excluded in the others. Four of the five patients belonged to the 31 allogeneic and one to the 26 autologous SCT patients. In patients with only one positive GM test none developed signs of IFI and only one received empirical amphotericin B.\n With the currently used preventative and prophylactic measures, IFI is uncommon in children with high-risk for infection. Regular screening for GM could be useful among allogeneic SCT patients and two positive samples should prompt further investigative procedures and pre-emptive antifungal therapy.\n (c) 2006 Wiley-Liss, Inc." ]

[ "16084925", "12694632", "16708003", "22032247", "18237352", "15066200", "15249520", "15113492", "21924563" ]

[ "Can a facilitated programme promote effective multidisciplinary audit in secondary care teams? An exploratory trial.", "Randomised controlled trial of a theoretically grounded tailored intervention to diffuse evidence-based public health practice [ISRCTN23257060].", "Cluster randomized controlled trial of the effectiveness of audit and feedback and educational outreach on improving nursing practice and patient outcomes.", "Implementing collaborative care for depression treatment in primary care: a cluster randomized evaluation of a quality improvement practice redesign.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].", "Achieving involvement: process outcomes from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.", "Adoption, reach and effectiveness of computer-based, practitioner delivered and combined smoking interventions in general medical practices: a three-arm cluster randomized trial." ]

[ "This 24-month exploratory study evaluated whether a 6-month programme supported by a trained external facilitator was feasible, acceptable and led to the adoption of a multidisciplinary approach to audit by secondary care staff. Undertaken in five acute hospital sites in the East Midlands UK, 22 multidisciplinary teams were randomised to either an intervention or control arm. Employing mixed methods, a range of outcomes, including collaborative behaviour, was measured. The intervention was feasible and acceptable to staff. Involvement in the facilitated programme had a positive impact on self-reported knowledge (P=0.000 post-intervention and at 4-months follow-up), skills (P=0.000 post-intervention and P=0.02 at 4-months follow-up) and attitudes (P<0.01 post-intervention), appeared to have some influence on improving self-reported (P<0.05 post-intervention) and observed collaborative behaviour (P=0.01) and led to better quality audit resulting in measurable improvements to care. Improved collaborative behaviour may have resulted from an increase in assertive behaviour by nurses. Research to test approaches to support teams to work effectively together is currently hampered by a lack of suitable research instruments and needs addressing before main (phase 111) trials are undertaken.", "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.", "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.", "Meta-analyses show collaborative care models (CCMs) with nurse care management are effective for improving primary care for depression. This study aimed to develop CCM approaches that could be sustained and spread within Veterans Affairs (VA). Evidence-based quality improvement (EBQI) uses QI approaches within a research/clinical partnership to redesign care. The study used EBQI methods for CCM redesign, tested the effectiveness of the locally adapted model as implemented, and assessed the contextual factors shaping intervention effectiveness.\n The study intervention is EBQI as applied to CCM implementation. The study uses a cluster randomized design as a formative evaluation tool to test and improve the effectiveness of the redesign process, with seven intervention and three non-intervention VA primary care practices in five different states. The primary study outcome is patient antidepressant use. The context evaluation is descriptive and uses subgroup analysis. The primary context evaluation measure is naturalistic primary care clinician (PCC) predilection to adopt CCM.For the randomized evaluation, trained telephone research interviewers enrolled consecutive primary care patients with major depression in the evaluation, referred enrolled patients in intervention practices to the implemented CCM, and re-surveyed at seven months.\n Interviewers enrolled 288 CCM site and 258 non-CCM site patients. Enrolled intervention site patients were more likely to receive appropriate antidepressant care (66% versus 43%, p = 0.01), but showed no significant difference in symptom improvement compared to usual care. In terms of context, only 40% of enrolled patients received complete care management per protocol. PCC predilection to adopt CCM had substantial effects on patient participation, with patients belonging to early adopter clinicians completing adequate care manager follow-up significantly more often than patients of clinicians with low predilection to adopt CCM (74% versus 48%%, p = 0.003).\n Depression CCM designed and implemented by primary care practices using EBQI improved antidepressant initiation. Combining QI methods with a randomized evaluation proved challenging, but enabled new insights into the process of translating research-based CCM into practice. Future research on the effects of PCC attitudes and skills on CCM results, as well as on enhancing the link between improved antidepressant use and symptom outcomes, is needed.\n ClinicalTrials.gov: NCT00105820.", "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation.", "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.", "A consulting method known as 'shared decision making' (SDM) has been described and operationalized in terms of several 'competences'. One of these competences concerns the discussion of the risks and benefits of treatment or care options-'risk communication'. Few data exist on clinicians' ability to acquire skills and implement the competences of SDM or risk communication in consultations with patients.\n The aims of this study were to evaluate the effects of skill development workshops for SDM and the use of risk communication aids on the process of consultations.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. Half the consultations were randomly selected for audio-taping, of which 352 patients attended and were audio-taped successfully. After baseline, participating doctors were randomized to receive training in (i) SDM skills or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were allocated randomly to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations were audio-taped from each phase. Raters (independent, trained and blinded to study phase) assessed the audio-tapes using a validated scale to assess levels of patient involvement (OPTION: observing patient involvement), and to analyse the nature of risk information discussed. Clinicians completed questionnaires after each consultation, assessing perceived clinician-patient agreement and level of patient involvement in decisions. Multilevel modelling was carried out with the OPTION score as the dependent variable, and rater, consultation and clinician levels of data, standardized by rater within clinician.\n Following each of the interventions, the clinicians significantly increased their involvement of patients in decision making (OPTION score increased by 10.6 following risk communication training [95% confidence interval (CI) 7.9 -13.3; P < 0.001] and by 12.9 after SDM skill development (95% CI 10 -15.8, P < 0.001), a moderate effect size. The level of involvement achieved by the risk communication aids was significantly increased by the subsequent introduction of the skill development workshops (7.7 increase in OPTION score, 95% CI 3.4-12; P < 0.001). The alternative sequence (skills followed by risk communication aids) did not achieve this effect. The use of most risk information formats increased after the provision of specific risk communication aids (P < 0.001). Clinicians using the risk communication tools perceived significantly higher patient and clinician agreement on treatment (P < 0.001), patient satisfaction with information (P < 0.01), clinician satisfaction with decision (P < 0.01) and general overall satisfaction with the consultation (P < 0.001) than those who were exposed to SDM skill development workshops.\n These clinicians were able to acquire the skills to implement SDM competences and to use risk communication aids. Each intervention provided independent effects. Further progress towards greater patient involvement in health care decision making is possible, and skill development in this area should be incorporated into postgraduate professional development programmes.", "Primary care clinicians have a considerable amount of contact with patients suffering from long-term mental illness. The United Kingdom's National Health Service now requires general practices to contribute more systematically to care for this group of patients.\n To determine the effects of Mental Health Link, a facilitation-based quality improvement programme designed to improve communication between the teams and systems of care within general practice. Design of study: Exploratory cluster randomised controlled trial.\n Twenty-three urban general practices and associated community mental health teams.\n Practices were randomised to service development as usual or to the Mental Health Link programme. Questionnaires and an audit of notes assessed 335 patients' satisfaction, unmet need, mental health status, processes of mental and physical care, and general practitioners' satisfaction with services and beliefs about service development. Service use and intervention costs were also measured.\n There were no significant differences in patients' perception of their unmet need, satisfaction or general health. Intervention patients had fewer psychiatric relapses than control patients (mean = 0.39 versus 0.71, respectively, P = 0.02) but there were no differences in documented processes of care. Intervention practitioners were more satisfied and services improved significantly for intervention practices. There was an additional mean direct cost of pound 63 per patient with long-term mental illness for the intervention compared with the control.\n Significant differences were seen in relapse rates and practitioner satisfaction. Improvements in service development did not translate into documented improvements in care. This could be explained by the intervention working via the improvements in informal shared care developed through better link working. This type of facilitated intervention tailored to context has the potential to improve care and interface working.", "Brief advice for smoking patients has not been sufficiently integrated in routine care. Computer-based interventions emerged as a time saving option that might help to exhaust the potential population impact of the general practice setting.\n 151 practices were randomly assigned to one of three intervention programs consisting in the delivery of: (1) brief advice by the practitioner; (2) individually tailored computer-generated letters; or (3) a combination of both interventions. We assessed three dimensions of population impact: (1) adoption, i.e., the rate of practices participating in the program; (2) reach, measured as the number of interventions provided within 7 months; (3) effectiveness, measured as smoking abstinence at 12-months follow-up.\n Among the practices, 70% adopted the program with no significant differences across study groups. Treatment was provided to 3086 adult smokers. Negative binomial regression analysis revealed that the number of interventions provided was higher in practices allocated to the tailored letter and combination intervention groups by 215% (p<.01) and 127% (p=.02), respectively, compared to the brief advice intervention group. Among the patients who received the combination of both intervention, the odds of point abstinence from smoking was increased by 65% (p=.02) and 32% (p=.01) compared to the brief advice and tailored letters intervention respectively. Comparing the number of abstinent patients at follow-up revealed that the tailored letter and combination interventions were superior to the brief advice intervention.\n Computer-based interventions alone or in addition to conventional practitioner-delivered advice can foster the participation of general medical practices in tobacco control.\n Copyright © 2011 Elsevier Ireland Ltd. All rights reserved." ]

[ "3904456", "2008006", "19517694", "16730113", "11914565", "7943103", "15913621", "10192481", "12706276" ]

[ "Prophylactic intrapartum amnioinfusion in patients with preterm premature rupture of membranes.", "A prospective, randomized evaluation of intrapartum amnioinfusion. Fetal acid-base status and cesarean delivery.", "Amnioinfusion for relief of recurrent severe and moderate variable decelerations in labor.", "Transcervical intrapartum amnioinfusion for preterm premature rupture of the membranes.", "Influence of volume preloading on uteroplacental and fetal circulation during spinal anaesthesia for caesarean section in uncomplicated singleton pregnancies.", "Prophylactic amnioinfusion for meconium-stained amniotic fluid.", "Therapeutic amnioinfusion for intrapartum fetal distress using a pediatric feeding tube.", "Amnioinfusion in term labor with low amniotic fluid due to rupture of membranes: a new indication.", "Prophylactic transcervical amnioinfusion in laboring women with oligohydramnios." ]

[ "Patients with preterm premature rupture of the membranes are at increased risk to develop intrapartum variable decelerations and fetal distress. Short-term saline solution amnioinfusion may be of benefit in the treatment of variable or prolonged decelerations once they appear. In an effort to assess the benefit of prophylactic amnioinfusion, patients with preterm premature rupture of the membranes were studied during a 1-year period in a prospective randomized manner. Patients receiving prophylactic amnioinfusion had significantly decreased incidence and severity of variable decelerations in the first stage of labor (p less than 0.005). In the second stage of labor, the incidence of severe (p less than 0.005) and total (p less than 0.001) decelerations was also decreased in the treatment group. The umbilical arterial pH at delivery was significantly lower (p less than 0.001) as was the umbilical venous pH (p less than 0.005) in the newborn infants of control patients compared with those of patients receiving amnioinfusion. This suggests that prophylactic intrapartum amnioinfusion is of significant benefit in reducing the incidence of variable decelerations and improving the metabolic state in newborn infants born to women with preterm premature rupture of the membranes.", "Pregnancies with decreased amniotic fluid volume are prediposed to umbilical cord compression and variable fetal heart rate declerations. Intrapartum amnioinfusion has been utilized in an effort to reduce cord compression. Previous studies suggested that amnioinfusion may improve the fetal metabolic state and reduce the incidence of cesarean delivery in selected patients. In this study the hypothesis was tested that intrapartum amnioinfusion will relieve cord compression in pregnancies complicated by oligohydramnios and will result in a reduced incidence of fetal intolerance to labor as well as improved fetal acid-base status at delivery. Thirty-five patients fulfilling the inclusion criteria were randomized to either the control (n = 16) or amnioinfusion treatment group (n = 19). Analysis of the data suggested that the two groups were similar for the perinatal parameters evaluated. No differences were observed in the umbilical artery blood gas analysis or incidence of cesarean section between the two groups. Intrapartum amnioinfusion does not appear to improve the perinatal outcome in pregnancies with oligohydramnios.", "To determine whether intrapartum amnioinfusion (AI) relieves recurrent moderate and severe variable decelerations in laboring women with clear or grade I meconium-stained amniotic fluid and reduces cesarean section rate for fetal distress.\n A randomized controlled trial was conducted in labor unit of Christian Medical College Hospital, Vellore, India, between October 2003 and September 2004. Women were randomized to receive AI (group I) and not to receive it (group II).\n A total of 150 women (75 in each group) were included in the study. There was significant relief of variable decelerations in group I and no difference in overall cesarean section rate but significant reduction in cesarean section rate for fetal distress in group I, and significant reduction in cesarean section rate for fetal distress in nulliparous women of group I. Neonatal acidemia was also significantly reduced in the nulliparous women receiving AI. The duration of maternal postpartum hospital stay was significantly reduced in group I. There were no adverse maternal or neonatal outcomes.\n AI was a beneficial therapeutic intervention in women patients showing fetal distress in first stage of labor, and it reduced cesarean section for fetal distress and neonatal acidemia.", "To investigate the effect of transcervical amnioinfusion on the management of labour and neonatal outcomes in preterm premature rupture of the membranes.\n This clinical trial included 86 patients with premature rupture of the membranes between weeks 27 and 35 of gestation. Patients were randomly assigned to receive amnioinfusion via a two-way catheter or to the control group. Clinical management was otherwise the same in both groups.\n Amnioinfusion decreased the frequency of variable decelerations in fetal heart rate (27.9% versus 53.5%, p<0.05) and the rate of obstetric interventions motivated by nonreassuring fetal status (13.6% versus 52.4%, p<0.05). At delivery, pH values were significantly higher in the treatment group than in the conventionally managed control group (median 7.29 versus 7.27).\n Intrapartum transcervical amnioinfusion for preterm premature rupture of the membranes reduced the number of interventions needed because of nonreassuring fetal status, and improved neonatal gasometric values without increasing maternal or fetal morbidity.", "Effects of volume preloading during spinal anaesthesia for elective caesarean section on maternal blood pressure, feto-maternal circulation and fetal outcome.\n In a pilot study a randomised trial was performed in 22 healthy women with uncomplicated, singleton pregnancies at 36-40 weeks of gestation undergoing elective caesarean section under spinal anaesthesia. In the low volume group (group A) patients received 150 ml of crystalloid solution for preloading, in the high volume group (group B) they were given 15 ml/kg of crystalloid solution for preloading before the initiation of spinal anaesthesia. Maternal blood pressure was monitored intermittently. Hypotension was defined as a decrease in systolic pressure to less than 80% of the baseline value. The Doppler flow evaluation consisted of measurements from the uterine artery at the placental site, fetal umbilical artery and fetal middle cerebral artery. Pulsatility indices were derived before and after fluid preloading, and when spinal anaesthesia was established. The neonatal outcome was assessed by Apgar scores, arterial acid base status and neurologic and adaptive capacity scores (NACS).\n The incidence of maternal hypotension in both groups was 45.5% (n = 10); 3 cases occurred in group A compared to 7 cases in group B (n.s.). There was no evidence that the high dose volume is useful in preventing maternal hypotension. The pulsatility indices of uterine arteries, umbilical arteries and middle cerebral arteries were not altered. Statistical analysis showed no changes in neonatal outcome concerning umbilical arterial pH, Apgar score and NACS (n.s.) between groups A and B.\n Our preliminary results suggest that high dose crystalloid volume preloading has no preventive function in the avoidance of maternal hypotension in healthy parturients undergoing elective caesarean section under spinal anaesthesia, and shows no harmful effects on neonatal outcome as long as maternal hypotension is corrected immediately. However, the statistical significance may reflect the small sample size, and larger series are needed before changing the current management.\n Copyright 2002 S. Karger AG, Basel", "Previous studies have demonstrated reduced perinatal morbidity in patients receiving amnioinfusion for meconium-stained amniotic fluid compared with control patients receiving no amnioinfusion. Because amnioinfusion for variable fetal heart rate decelerations has become accepted care, we sought to determine the benefit of prophylactic amnioinfusion for meconium compared with standard care, incorporating therapeutic amnioinfusion for variable decelerations.\n Ninety-three term patients with moderate to heavy meconium and no variable fetal heart rate decelerations were randomized to immediate prophylactic amnioinfusion (600 ml saline solution bolus followed by 3 ml/min) or to standard care (including therapeutic amnioinfusion for variable decelerations developing later). All babies had DeLee suctioning on delivery of the head. Laryngeal cords were visualized and tracheal suctioning performed when meconium was seen below the cords. Statistical comparisons were performed using Student t test, Fisher's exact test, or chi 2 analysis.\n There were no significant differences in the incidence of operative delivery, fetal distress, or meconium below the cords or in newborn Apgar scores and umbilical artery gas values between the amnioinfusion (n = 43) and control (n = 50) patients. There were four cases of meconium aspiration, three in the amnioinfusion group, one in the standard care group. The rate of endometritis-chorioamnionitis was higher (p = 0.3) in the amnioinfusion (16%) than in the control group (8%), although time from ruptured membranes to delivery (8.5 hours vs 7.3 hours) and duration of intrauterine monitoring (6.1 hours vs 5.3 hours) were not different.\n Although amnioinfusion does dilute amniotic meconium, prophylactic amnioinfusion for meconium in the absence of variable decelerations remains controversial. Prophylactic amnioinfusion in term pregnancies did not improve perinatal outcome and increased the risk for chorioamnionitis-endometritis. Together with recent reports, the current data suggest that the benefit of amnioinfusion for meconium-stained amniotic fluid is a result of the alleviation of variable fetal heart rate decelerations rather than meconium dilution.", "To evaluate the role of therapeutic amnioinfusion using a pediatric feeding tube in cases of intrapartum fetal distress.\n A randomized clinical trial including 438 women admitted in labor at Assiut University Hospital with nonreassuring fetal heart rate tracing. Using sealed opaque envelopes, the women were randomized to 2 groups. In the amnioinfusion group they underwent transcervical amnioinfusion (1000 mL of warmed sterile saline solution) in addition to conventional treatment. In the control group they received conventional treatment only. The primary outcome was cesarean section rate for fetal distress. The secondary outcomes were neonatal and maternal complications.\n The amnioinfusion group showed a significant reduction in the rate of cesarean section for fetal distress (relative risk [RR], 0.7; 95% confidence interval [CI], 0.6-0.83), and a 30% reduction in abnormal fetal heart rate patterns (RR, 0.7; 95% CI, 0.6-0.83). Significantly fewer newborns had Apgar scores less than 7 at 1 and 5 min in the amnioinfusion group than in the control group (RR, 0.38; 95% CI, 0.26-0.55 and RR, 0.31; 95% CI, 0.15-0.64, respectively). Significantly fewer newborns had meconium below the vocal cords in the amnioinfusion group than in the control group (RR, 0.36; 95% CI, 0.13-0.97). Moreover, 14 newborns in the amnioinfusion group needed admission to the intensive care unit vs. 31 newborns in the control group. There were no significant differences between the 2 groups regarding the incidence rates of uterine hypertonus and maternal temperature higher than 38 degrees C.\n Therapeutic amnioinfusion is a simple and effective intervention that reduces the rates of cesarean section for intrapartum nonreassuring fetal heart tracing. In under-resourced settings, it can be performed using inexpensive catheters.", "The null hypothesis was that the use of intrapartum amnioinfusion to induce term labor because of premature rupture of membranes when labor was complicated by low amniotic fluid volume due to vaginal loss would not improve fetal heart rate patterns, decrease the incidence of operative delivery, or improve neonatal acid-base status.\n 200 term pregnancies with low amniotic fluid due to vaginal loss were randomly chosen to receive intrapartum amnioinfusion or standard obstetric care without amnioinfusion. Fetal heart rate pattern, method of delivery and neonatal acid-base status were compared with Student's t test, chi-squared analysis, Mann-Whitney U- or Fisher's exact test.\n When amnioinfusion was used, the fetuses had lower rates of variable (74 vs. 91%, P<0.01) or late (26 vs. 58%, P<0.001) decelerations. Spontaneous deliveries were more frequent (77 vs. 59%, P<0.01) and cesarean sections less frequent (3 vs. 10%, P<0.05). Mean umbilical arterial (7.24+/-0.07 vs. 7.21+/-0.08, P<0.01) and venous (7.31+/-0.06 vs. 7.28+/-0.08, P<0.01) pH were significantly higher in newborns with amnioinfusion, and babies in this group had lower rates of neonatal acidemia of arterial (22 vs. 36%, P<0.005) or venous (13 vs. 26%, P<0.005) origin.\n Amnioinfusion improved fetal heart rate pattern, lowered the incidence of operative delivery, and improved neonatal acid-base status in term labor complicated by low amniotic fluid due to vaginal loss.", "Evaluation of prophylactic intrapartum amnioinfusion in women with oligohydramnios.\n Assiut University Hospital during the period from February 2000 to September 2001, 160 laboring women with oligohydramnios [amniotic fluid index (AFI) </=5 cm] were randomized into: amnioinfusion and control groups. Inclusion criteria were: term singleton gestation, vertex presentation, cervical dilatation <4 cm, and assuring fetal heart rate (FHR). Trans-cervical amnioinfusion was done with warmed normal saline.\n there was a significant increase in AFI after amnioinfusion (P<0.001). The amnioinfusion group showed lower cesarean section rate for fetal distress (P=0.003), lower incidence of abnormal FHR (P=0.006), fewer neonates with Apgar score <7 at 1 min (P<0.001), and 5 min (P=0.009), meconium below vocal cords (P<0.001), umbilical arterial pH<7.1 (P=0.003), and significantly shorter hospital stay (P=0.02).\n Prophylactic trans-cervical amnioinfusion is a simple, safe and effective procedure." ]

[ "17650935", "17164546", "14526151", "16149365", "11882400", "12358242", "9448611", "9351723", "18328440" ]

[ "[Total enteral nutrition vs. total parenteral nutrition in patients with severe acute pancreatitis].", "A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition.", "A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II > or =6).", "2004 MacLean-Mueller prize enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment.", "Early nasojejunal feeding in acute pancreatitis is associated with a lower complication rate.", "Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study.", "Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial.", "A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy.", "Dietary counseling versus dietary supplements for malnutrition in chronic pancreatitis: a randomized controlled trial." ]

[ "To compare the efficacy of early total enteral nutrition (TEN) vs. total parenteral nutrition (TPN) in patients with severe acute pancreatitis (SAP).\n A total of 22 consecutive patients with SAP were randomized to receive TPN (group I) or TEN (group II). SAP was defined applying APACHE II score, C-reactive protein (CRP) measurements and/or Balthazar CT scan score. Acute inflammatory response (CRP, TNF-a, IL-6), visceral proteins (pre-albumin, albumin), complications (systemic inflammatory response syndrome, multiorgan failure, infections), surgical interventions, length of hospital stay and mortality were evaluated.\n No significant differences were found between the two groups in the APACHE II score, in CRP, TNF-a and IL-6 concentrations or in pre-albumin and albumin levels over the first 10 days. Seven patients in group I and 4 in group II suffered severe complications. Three patients in group I required surgical intervention. Length of hospital stay was alike in the two groups. Two patients from group I died in the course of the hospitalization.\n SAP patients with TEN feeding showed a tendency towards a better outcome than patients receiving TPN.", "Infectious complications are the main cause of late death in patients with acute pancreatitis. Routine prophylactic antibiotic use following a severe attack has been proposed but remains controversial. On the other hand, nutritional support has recently yielded promising clinical results. The aim of study was to compare enteral vs. parenteral feeding for prevention of infectious complications in patients with predicted severe acute pancreatitis.\n We screened 466 consecutive patients with acute pancreatitis. A total of 70 patients with objectively graded severe acute pancreatitis were randomly allocated to receive either total enteral nutrition (TEN) or total parenteral nutrition (TPN), within 72 h of onset of symptoms. Baseline characteristics were well matched in the two groups.\n The incidence of pancreatic infectious complications (infected pancreatic necrosis, pancreatic abscess) was significantly lower in the enterally fed group (7 vs. 16, p = 0.02). In the TEN group, 7 patients developed multiple organ failure whereas 17 parenterally fed patients developed multiple organ failure (p = 0.02). Overall mortality was 20% with two deaths in the TEN group and twelve in the TPN group (p < 0.01).\n Early TEN could be used as prophylactic therapy for infected pancreatic necrosis since it significantly decreased the incidence of pancreatic infectious complications as well as the frequency of multiple organ failure and mortality.\n Copyright 2006 S. Karger AG, Basel.", "Total enteral nutrition (TEN) within 48 h of admission has recently been shown to be safe and efficacious as part of the management of severe acute pancreatitis. Our aim was to ascertain the safety of immediate TEN in these patients and the effect of TEN on systemic inflammation, psychological state, oxidative stress, plasma glutamine levels and endotoxaemia.\n Patients admitted with predicted severe acute pancreatitis(APACHE II score >5) were randomised to total enteral (TEN; n = 8) or total parenteral nutrition (TPN; n = 9). Measurements of systemic inflammation (C-reactive protein), fatigue (visual analogue scale), oxidative stress (plasma thiobarbituric acid-reactive substances), plasma glutamine and anti-endotoxin IgG and IgM antibody concentrations were made on admission and repeated on days 3 and 7 thereafter. Clinical progress was monitored using APACHE II score. Organ failure and complications were recorded.\n All patients tolerated the feeding regime well with few nutrition-related complications. Fatigue improved in both groups but more rapidly in the TEN group. Oxidative stress was high on admission and rose by similar amounts in both groups. Plasma glutamine concentrations did not change significantly in either group. In the TPN group, 3 patients developed respiratory failure and 3 developed non-respiratory single organ failure. There were no such complications in the TEN group. Hospital stay was shorter in the TEN group [7(4-14) vs. 10 (7-26) days; p = 0.05] as was time to passing flatus and time to opening bowels [1 (0-2) vs. 2 (1-5)days; p = 0.01]. The cost of TEN was considerably less than of TPN.\n Immediate institution of nutritional support in the form of TEN is safe in predicted severe acute pancreatitis. It is as safe and as efficacious as TPN and may be beneficial in the clinical course of this disease.", "The optimal route of nutrition in severe pancreatitis is controversial. Parenteral nutrition (PN) is preferred, but enteral nutrition (EN) promises to attenuate inflammation and prevent sepsis. We hypothesized that EN was at least equivalent to PN in reducing inflammation, providing effective nutrition and being cost-effective.\n We conducted a randomized controlled trial comparing PN to EN in pancreatitis in an academic, multi-institutional, tertiary care health system. We screened 728 consecutive patients. Twenty-eight patients with a Ranson's score greater than 2 who did not tolerate clear fluids 4 days after admission were randomized: 18 to PN and 10 to EN. Both groups were provided daily 105 kJ (25 kcal)/kg and 1.5 g/kg of protein, respectively, until they could tolerate a regular diet.\n C-reactive protein in EN patients was reduced by 50% 5 days faster than PN patients (Wilcoxon test, p = 0.09). Both groups received a similar number of kilojoules and achieved near normal prealbumin and 24-hour urinary nitrogen values. Neither regimen caused a change in cholecystokinin levels. Overall mortality was 4.9% (3 patients in the PN group). In 5 patients (4 PN, 1 EN) there were infected pancreatic collections. Nine EN patients dislodged the nasojejunal tube. EN had an average cost of dollar 1375 per patient compared with dollar 2608 for PN (p = 0.08). After sensitivity analysis, EN cost dollar 957 compared with dollar 2608 for PN (p = 0.03).\n EN or PN is safe and provides adequate nutrition in severe pancreatitis. EN shows a trend toward faster attenuation of inflammation, with fewer septic complications and is the dominant therapy in terms of cost-effectiveness. This study favours EN for nutritional support in severe pancreatitis.", "We investigated the effect of early jejunal feeding on septic complications and mortality rate in patients with acute pancreatitis in a two-phase, prospective, controlled study.\n In the first, randomized phase of the study, conventional parenteral nutrition was compared with early (within 24-72 h after the onset of symptoms) enteral nutrition. Of 89 patients admitted with acute pancreatitis, 48 patients were randomized into a parenteral group (Rindex 10, Infusamin S, Intralipid 10%; 30 kcal/kg) and 41 patients into an enteral group (jejunal tube feeding; Survimed OPD; 30 kcal/kg).\n The rate of septic complications (infected pancreatic necrosis, abscess) was lower in the enteral group (P = 0.08, chi(2) test). In the second phase of the study, early jejunal feeding was combined with prophylactic imipenem (Tienam, 500 mg intravenously twice each day) when necrosis of the pancreas was detected by abdominal computed tomography. When the outcomes of 92 patients in the third group were compared with those of patients in the parenteral group, the rate of septic complications decreased significantly (P = 0.03). Multiple organ failure (P = 0.14) and mortality (P = 0.13) tended to decrease.\n We believe that the combination of early enteral nutrition and selective, adequate antibiotic prophylaxis may prevent multiple organ failure in patients with acute pancreatitis.", "The aims of this study were to define the indications for, and to evaluate the cost-effectiveness of, nutritional support in patients with acute pancreatitis.\n All admissions during the 12-month period from January through December 2000, were entered into a common management protocol consisting of an initial 48-h fast with i.v. fluids and analgesics. After 48 h, those patients who were improving were restarted on oral feeding (group O). The remaining patients were randomized to receive nasojejunal (group EN) or parenteral feeding (group TPN). The randomization study was continued until 50 patients had been accrued. Outcomes in the three groups were compared with respect to length of hospital stay, duration of feeding, complications, and hospital costs.\n A total of 156 admissions were evaluated in the first 12 months. Of these, 87% patients had mild disease, 10% moderate, and 3% severe; 62% were related to alcohol abuse, 18% gallstones, and 8% idiosyncratic drug reactions. Of the patients, 75% improved on 48 h bowel rest and i.v. fluids, and were discharged within 4 days. The remainder were randomized to jejunal elemental (n = 26) or parenteral (n = 27) feeding. Duration of feeding was shorter with EN (6.7 vs 10.8 days, p < 0.05) and nutrition costs were lower, representing an average cost saving of $2362.00 per patient fed. EN was less effective in meeting estimated nutritional requirements (54 vs 88%, p < 0.0001), but metabolic (p < 0.003) and septic complications (p = 0.01) were lower. Subgroup analysis of patients with severe disease showed similar findings.\n Despite concerns that metabolic expenditure is increased and that food-stimulated pancreatic secretion might exacerbate the disease process, hypocaloric enteral feeding seems to be safer and less expensive than parenteral feeding and bowel rest in patients with acute pancreatitis.", "Parenteral nutrition is well established for providing nutritional support in acute pancreatitis while avoiding pancreatic stimulation. However, it is associated with complications and high cost. Benefits of enteral feeding in other disease states prompted a comparison of early enteral feeding with total parenteral nutrition in this clinical setting.\n Thirty-eight patients with acute severe pancreatitis were randomized into two groups. The first (n = 18) received enteral nutrition through a nasoenteric tube with a semi-elemental diet, while the second group (n = 20) received parenteral nutrition through a central venous catheter. Safety was assessed by clinical course of disease, laboratory findings and incidence of complications. Efficacy was determined by nitrogen balance. The cost of nutritional support was calculated.\n Enteral feeding was well tolerated without adverse effects on the course of the disease. Patients who received enteral feeding experienced fewer total complications (P < 0.05) and were at lower risk of developing septic complications (P < 0.01) than those receiving parenteral nutrition. The cost of nutritional support was three times higher in patients who received parenteral nutrition.\n This study suggests that early enteral nutrition should be used preferentially in patients with severe acute pancreatitis.", "The purpose of the study was to determine whether early postoperative enteral feeding with an immune-enhancing formula (IEF) decreases morbidity, mortality, and length of hospital stay in patients with upper gastrointestinal (GI) cancer.\n Early enteral feeding with an IEF has been associated with improved outcome in trauma and critical care patients. Evaluable data documenting reduced complications after major upper GI surgery for malignancy with early enteral feeding are limited.\n Between March 1994 and August 1996, 195 patients with a preoperative diagnosis of esophageal (n = 23), gastric (n = 75), peripancreatic (n = 86), or bile duct (n = 11) cancer underwent resection and were randomized to IEF via jejunostomy tube or control (CNTL). Tube feedings were supplemented with arginine, RNA, and omega-3 fatty acids, begun on postoperative 1, and advanced to a goal of 25 kcal/kg per day. The CNTL involved intravenous crystalloid solutions. Statistical analysis was by t test, chi square, or logistic regression.\n Patient demographics, nutritional status, and operative factors were similar between the groups. Caloric intake was 61% and 22% of goal for the IEF and CNTL groups, respectively. The IEF group received significantly more protein, carbohydrate, lipids and immune-enhancing nutrients than did the CNTL group. There were no significant differences in the number of minor, major, or infectious wound complications between the groups. There was one bowel necrosis associated with IEF requiring reoperation. Hospital mortality was 2.5% and median length of hospital stay was 11 days, which was not different between the groups.\n Early enteral feeding with an IEF was not beneficial and should not be used in a routine fashion after surgery for upper GI malignancies.", "Up to 50% of patients with chronic pancreatitis (CP) are malnourished. There are limited data on the role of dietary intervention in improving the nutritional status of such patients. The aim was to compare the efficacy of medium chain triglyceride (MCT)-enriched commercial dietary supplements with dietary counseling for homemade food in the management of malnutrition in patients with CP.\n In a randomized controlled trial, consecutive undernourished patients with CP (body mass index [BMI] <18.5 kg/m(2)) at a tertiary care hospital were randomized to receive either dietary counseling for regular homemade food or commercial MCT-enriched dietary supplements for a period of 3 months to compensate for the dietary calorie deficit. All patients received standard management for CP including pancreatic enzyme supplements. Primary outcome measure was improvement in BMI.\n Sixty malnourished patients with CP were randomized to counseling group (n = 29; mean age, 32 +/- 10 years; male, 83%) and supplementation group (n = 31; mean age, 28 +/- 10 years; male, 84%). BMI increased in both the counseling group and supplementation group (17.2 +/- 1.7 vs 18.1 +/- 1.8 kg/m(2), P = .001; 16.7 +/- 1.6 vs 18.2 +/- 1.6 kg/m(2), P = .001). There were similar improvements in triceps skinfold thickness, dietary intake, fecal fat, and pain score during a period of 3 months in both groups. There was, however, no significant difference between the counseling and supplementation groups with regard to any of the outcome measures.\n Dietary counseling for a balanced homemade diet is as good as commercial food supplements in improving malnutrition in patients with CP." ]

[ "17045832", "16697231", "19951217", "17173219", "11305547", "18001442", "8014510", "9524997", "10908773" ]

[ "Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis.", "Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial.", "Changes in the vaginal microenvironment with metronidazole treatment for bacterial vaginosis in early pregnancy.", "A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis.", "Antibiotic prophylaxis to prevent post-abortal upper genital tract infection in women with bacterial vaginosis: randomised controlled trial.", "Treatment options for bacterial vaginosis in patients at high risk of preterm labor and premature rupture of membranes.", "A double-blind placebo-controlled trial of single-dose intravaginal versus single-dose oral metronidazole in the treatment of trichomonal vaginitis.", "A pilot study of metronidazole vaginal gel versus oral metronidazole for the treatment of Trichomonas vaginalis vaginitis.", "Vaginal clindamycin and oral metronidazole for bacterial vaginosis: a randomized trial." ]

[ "Bacterial vaginosis (BV) is particularly common in black women, and in Nigeria it is often caused by Mycoplasma, as well as Atopobium, Prevotella and Gardnerella sp. Antimicrobial metronidazole oral therapy is poorly effective in eradicating the condition and restoring the Lactobacillus microbiota in the vagina. In this study, 40 women diagnosed with BV by discharge, fishy odor, sialidase positive test and Nugent Gram stain scoring, were randomized to receive either two dried capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each night for 5 days, or 0.75% metronidazole gel, applied vaginally twice a day (in the morning and evening). Follow-up at day 6, 15 and 30 showed cure of BV in significantly more probiotic treated subjects (16, 17 and 18/20, respectively) compared to metronidazole treatment (9, 9 and 11/20: P=0.016 at day 6, P=0.002 at day 15 and P=0.056 at day 30). This is the first report of an effective (90%) cure of BV using probiotic lactobacilli. Given the correlation between BV and HIV, and the high risk of the latter in Nigeria, intravaginal use of lactobacilli could provide women with a self-use therapy, similar to over-the-counter anti-yeast medication, for treatment of urogenital infections.", "This study enrolled 125 premenopausal women diagnosed with bacterial vaginosis (BV) by presence of vaginal irritation, discharge and 'fishy' odor, and Nugent criteria and detection of sialidase enzyme. The subjects were treated with oral metronidazole (500 mg) twice daily from days 1 to 7, and randomized to receive oral Lactobacillus rhamnosus GR-1 (1 x 10(9)) and Lactobacillus reuteri RC-14 (1 x 10(9)) or placebo twice daily from days 1 to 30. Primary outcome was cure of BV as determined by normal Nugent score, negative sialidase test and no symptoms or signs of BV at day 30. A total of 106 subjects returned for 30-day follow-up, of which 88% were cured in the antibiotic/probiotic group compared to 40% in the antibiotic/placebo group (p<0.001). Of the remaining subjects, 30% subjects in the placebo group and none in the probiotic group had BV, while 30% in the placebo and 12% in the probiotic group fell into the intermediate category based upon Nugent score, sialidase result and clinical findings. High counts of Lactobacillus sp. (>10(5) CFU/ml) were recovered from the vagina of 96% probiotic-treated subjects compared to 53% controls at day 30. In summary, this study showed efficacious use of lactobacilli and antibiotic in the eradication of BV in black African women.", "Bacterial vaginosis (BV) is associated with preterm delivery, but there is little evidence that treatment improves pregnancy outcomes. We examined whether oral or vaginal metronidazole treatment for BV in early pregnancy was more effective in restoring the normal vaginal environment.\n This was a randomized controlled trial comparing oral and intravaginal metronidazole for treatment of BV in early pregnancy (<20 weeks). Vaginal samples collected at baseline and 4 weeks after treatment were evaluated using gram stain, culture, colorimetric detection of sialidase, and immunoassay for measurement of proinflammatory cytokines interleukins-1beta, -6, -8 (IL-1beta, IL-6, IL-8) and secretory leukocyte protease inhibitor (SLPI). We compared the effect of treatment between groups (using chi-square and t test) and within individuals (McNemar's test).\n Of 126 subjects, 108 (86%) completed follow-up (55 oral, 53 intravaginal). Of the study population, 34% achieved therapeutic cure, and this was not different between treatment groups. BV-associated bacteria were significantly reduced in both groups, but few subjects regained colonization with protective lactobacilli. Among women who achieved therapeutic cure, the level of IL-1beta dropped significantly (p < 0.001) and SLPI increased (p = 0.003). More women in the vaginal treatment group had undetectable sialidase after treatment (p = 0.013).\n Treatment with oral or intravaginal metronidazole in early pregnancy reduced colonization with BV-associated bacteria but was not effective in achieving therapeutic cure or in restoring healthy vaginal lactobacilli.", "Bacterial vaginosis (BV) is the most common cause of vaginitis worldwide. Currently recommended treatments have poor efficacy and are associated with high rates of BV recurrence. We examined whether a longer duration of treatment with metronidazole or combination therapy with metronidazole and azithromycin would enhance the cure rates for BV. In addition, we examined factors other than drug therapy associated with cure.\n Women with symptomatic BV (defined by a modified Amsel criteria) were enrolled in a 4-arm study that compared metronidazole for 7 days versus 14 days, plus or minus azithromycin on days 1 and 3. Data regarding interim behaviors were also obtained, as were vaginal specimens for Gram staining.\n At the first follow-up visit (7 days after the completion of therapy), there was a significant difference in cure rates among patients who received 7 days of metronidazole therapy, compared with those who received 14 days of therapy, combined across azithromycin therapy (P=.0003). There was no effect associated with azithromycin therapy. There were no differences in cure rates between any of the treatment groups at 21 days after completion of therapy. Abstinence or protected sex, refraining from douching, and a lower baseline Nugent score for the vaginal Gram stain were all significantly associated with cure.\n Cure rates for BV were significantly improved by 14 days of metronidazole treatment (compared with 7 days of treatment), but the effects were not sustained, suggesting that relapse or reinfection occurred. Combination therapy with the addition of azithromycin had no benefit. Lower baseline Nugent scores--presumably reflecting less complex vaginal flora--were significantly associated with cure, as was refraining from unprotected sex and from douching.", "To determine the prevalence of bacterial vaginosis in women undergoing first trimester suction termination of pregnancy and to evaluate the efficacy of metronidazole in reducing the risk of post abortal pelvic infection in women with bacterial vaginosis.\n Randomised double-blind placebo-controlled trial.\n Two teaching hospitals and one district general hospital.\n Two hundred and seventy-three women with bacterial vaginosis undergoing termination of pregnancy.\n Women with bacterial vaginosis, diagnosed using modified Spiegel's criteria, were individually randomised to receive either a 2 g metronidazole suppository or identical placebo per-operatively. Participants, doctors and investigators were blinded to treatment allocation. Participants were asked to complete a questionnaire about post-operative symptoms, visits to the general practitioner, antibiotic treatment, readmission to hospital, contraception and emotional response after one month.\n The prevalence of bacterial vaginosis was 29.3% (326/1,111). Intention-to-treat analysis showed that post-operative upper genital tract infection developed in 12/142 (8.5%) women allocated to metronidazole and 21/131 (16.0%) women randomised to placebo, a difference of 7.6% (95% confidence intervals -15.4 to +0.2%; relative risk 0.53. 0.27 to 1.03, P = 0.055). The effect of prophylaxis was similar when the analysis was restricted to women receiving the allocated treatment and with complete follow up. There was no difference in the risk of readmission to hospital and the frequencies of self reported symptoms in the two groups were similar.\n This randomised placebo-controlled trial among women with bacterial vaginosis provides weak evidence that metronidazole decreases the risk of upper genital tract infection after first trimester suction termination of pregnancy but a chance finding could not confidently be excluded. Large well-conducted randomised trials with long term outcome measures are now needed to determine the most effective antibiotic combinations and strategy for prevention of post-abortal pelvic infection.", "To estimate the efficacy of different therapeutic modalities on proven cases of bacterial vaginosis (BV) in patients at high risk of preterm labor and premature rupture of membranes.\n This was a longitudinal prospective comparative study set in the antenatal outpatient clinic of the department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, Assiut, Egypt. Four hundred and sixty-eight patients with a clinical picture of threatened preterm labor or at high risk of premature rupture of membranes in the third trimester were screened for BV. Positive BV was diagnosed in 156 patients. They were randomly classified into four equal groups according to the line of medical treatment. The treatments were: (i) oral metronidazole, (ii) clindamycin vaginal cream, (iii) oral clindamycin, or (iv) metronidazole vaginal suppositories. The effects of medical treatment on Amsel's criteria as well as maternal and fetal outcomes were measured.\n Based on Amsel's criteria, 156 patients (33.3%) were diagnosed with BV. There was a significant disappearance of vaginal discharge, with decreased percentages of pH > 4.5, positive amine test, and clue cells after treatment of BV in the four groups without any statistically significant difference between them. There were variable effects of the different treatments on increasing birthweight values, admission to neonatal intensive care units, and prolongation of the gestational age. Some maternal adverse effects have been recorded. There were significant improvements of the outcomes for oral metronidazole and clindamycin compared with outcomes for intravaginal metronidazole and clindamycin.\n Metronidazole and clindamycin achieve nearly equivalent cure rates when administered orally or vaginally in patients at high risk of preterm labor and premature rupture of membranes. Oral metronidazole is considered the drug of choice in treating BV due its high cure rate, better outcomes, and low cost.", "Since metronidazole is a mutagen in vitro, there is concern about the widespread systemic use of this drug in women with trichomoniasis, particularly those who are pregnant. A randomized, double-blind, placebo-controlled trial compared a single 2-g intravaginal dose of metronidazole cream with a single 2-g oral dose of metronidazole in patients with a culture positive for Trichomonas organisms. Of the 302 preenrollment cultures completed, 94 (31%) were positive. Sixty-one patients were enrolled in the study. Each received either oral placebo and intravaginal metronidazole or intravaginal placebo and oral metronidazole. Follow-up cultures were done on posttreatment day 3-5. Of the 53 evaluatable patients, 14 (50%) of 28 in the intravaginal group and 22 (88%) of 25 in the oral group were microbiologically cured (P = .0037). Single-dose intravaginal metronidazole is inferior to single-dose oral metronidazole and cannot be relied on as an alternative therapy.", "Trichomonas vaginalis is a common sexually transmitted pathogen. In the United States, oral metronidazole is the only officially sanctioned treatment option.\n This study was undertaken to compare the efficacy and safety of 0.75% metronidazole vaginal gel with that of oral metronidazole for the treatment of trichomonal vaginitis.\n Women with trichomoniasis were enrolled in this randomized, open-label pilot study of 0.75% metronidazole vaginal gel twice daily for 7 days compared with 7 days of generic oral metronidazole, 250 mg, three times daily. Patients were seen for follow-up visits 5 to 7 days and 21 to 28 days after the last dose of medication.\n Using culture for test of cure, trichomonal infection was eliminated in all 15 women treated with oral metronidazole and 7 (44%) of 16 women treated with intravaginal metronidazole. Adverse events were similar, except that there were more taste-related adverse events in the oral metronidazole group. Significant reductions in genitourinary symptoms were seen in both the oral and intravaginal groups.\n This study has shown that 0.75% metronidazole vaginal gel is not effective as a single agent for the treatment of trichomoniasis. Future studies may define a role for metronidazole gel for symptomatic relief in patients intolerant of oral medication or as adjunctive treatment with oral metronidazole for the management of patients infected with metronidazole-resistant strains of T. vaginalis.", "To compare the efficacy and safety of clindamycin vaginal ovules with oral metronidazole for treatment of bacterial vaginosis.\n Women with bacterial vaginosis received either 100-mg ovules of clindamycin (intravaginally for 3 consecutive days) plus placebo capsules (orally twice daily for 7 days) or metronidazole 500 mg (two 250-mg capsules orally twice daily for 7 days) plus placebo ovules (intravaginally for 3 consecutive days). The sample was determined prospectively to provide a probability of.84 of correctly concluding that the rate of success for clindamycin is not more than 15% less than the expected 75% success rate for metronidazole. Clinical outcome was determined on the basis of vaginal fluid amine odor and clue cells.\n Of the 399 patients enrolled, 233 could be evaluated for efficacy. Of those, 77 (68.1%) of 113 patients were cured with clindamycin, compared with 80 (66. 7%) of 120 who were cured with metronidazole (95% confidence interval -10.6%, 13.4%; P =.810). Treatment-related adverse events were reported more frequently in the metronidazole treatment group. Systemic symptoms, such as nausea and taste perversion, accounted for most of the difference between groups.\n A 3-day regimen of clindamycin, given as intravaginal ovules, was as effective as and better tolerated than a 7-day regimen of oral metronidazole 500 mg, given twice daily, for treatment of bacterial vaginosis." ]

[ "10342710", "12428233", "16974191", "8849355", "16373258", "15989411", "15529389", "18482290", "17050889" ]

[ "A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus.", "Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial.", "Improvement of sustained attention and visual and movement skills, but not clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial.", "Dehydroepiandrosterone in systemic lupus erythematosus. Results of a double-blind, placebo-controlled, randomized clinical trial.", "Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus.", "Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids.", "The effect of dehydroepiandrosterone on lumbar spine bone mineral density in patients with quiescent systemic lupus erythematosus.", "Effects of dehydroepiandrosterone supplementation on cognitive function and quality of life: the DHEA and Well-Ness (DAWN) Trial.", "DHEA in elderly women and DHEA or testosterone in elderly men." ]

[ "To determine if dehydroepiandrosterone (DHEA) is beneficial in severe systemic lupus erythematosus (SLE).\n A double-blinded, placebo-controlled, randomized clinical trial in 21 patients with severe and active SLE, manifestated primarily by nephritis, serositis or hematological abnormalities. In addition to conventional treatment with corticosteroids +/- immunosuppressives, patients received DHEA 200 mg/d vs. placebo for 6 months, followed by a 6-month open label period. The primary outcome was a prospectively defined responder analysis, based on a quantitatively specified improvement of the principal severe lupus manifestation at 6 months.\n Nineteen patients were available for evaluation at 6 months. Baseline imbalance between the groups was noted, with the DHEA group having greater disease activity at baseline (P<0.05 by physician's global assessment). Eleven patients were responders: 7/9 patients on DHEA vs. 4/10 patients on placebo (P<0.10). Of the secondary outcomes, mean improvement in SLE disease activity index (SLE-DAI) score was greater in the DHEA group (-10.3+/-3.1 vs. -3.9+/-1.4. P<0.07). Bone mineral density at the lumbo-sacral spine showed significant reduction in the placebo group, but was maintained in the DHEA group.\n DHEA therapy, when added to conventional treatment for severe SLE, may at most have a small added benefit with respect to lupus outcomes, but baseline imbalances in the study population limit the generalizability of the results. DHEA appears to have a protective effect with respect to corticosteroid-induced osteopenia in such patients.", "To evaluate the efficacy and tolerability of dehydroepiandrosterone (DHEA) at a dosage of 200 mg/day in adult women with active systemic lupus erythematosus (SLE).\n In a multicenter randomized, double-blind, placebo-controlled trial, 120 adult women with active SLE received oral DHEA (200 mg/day; n = 61) or placebo (n = 59) for 24 weeks. The primary end point was the mean change from baseline in the Systemic Lupus Activity Measure (SLAM) score at 24 weeks of therapy. Secondary end points included time to first flare, change in SLE Disease Activity Index (SLEDAI) score, and physician's and patient's global assessment scores at week 24.\n The two groups were well balanced for baseline characteristics. Mean reductions in SLAM scores from baseline were similar and were not statistically significantly different between treatment groups (DHEA -2.6 +/- 3.4 versus placebo -2.0 +/- 3.8, mean +/- SD). The number of patients with flares was decreased by 16% in the DHEA group (18.3% of DHEA-treated patients versus 33.9% of placebo-treated patients; P = 0.044, based on time to first flare). The mean change in the patient's global assessment was statistically significant between the two groups (DHEA -5.5 versus placebo 5.4; P = 0.005). The number of patients with serious adverse events, most of which were related to SLE flare, was significantly lower in DHEA-treated patients compared with placebo-treated patients (P = 0.010). Expected hormonal effects, including increased testosterone levels and increased incidence of acne, were observed. No life-threatening reactions or serious safety issues were identified during this study.\n The overall results confirm that DHEA treatment was well-tolerated, significantly reduced the number of SLE flares, and improved patient's global assessment of disease activity.", "Dehydroepiandrosterone (DHEA) augmentation has been reported, in a preliminary fashion, to be useful in the management of schizophrenia symptoms and side effects. In this study, the intention was to investigate the efficacy and safety of DHEA administration to ongoing antipsychotic medication in a multicenter, 12-week, double-blind, randomized, placebo-controlled, crossover trial.\n Fifty-five of 62 inpatients and outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia completed the trial. Patients were randomly allocated to 2 treatment groups receiving either DHEA (200 mg/d) or placebo for 6 weeks with the crossover between DHEA and placebo occurring after 6 weeks. Patients continued to receive their regular antipsychotic medication for the duration of the study.\n Compared with placebo, DHEA administration did not produce significant improvement in clinical symptoms, side effects, and quality-of-life scores. However, 6 weeks of DHEA administration (but not placebo) was associated with a significant improvement in Positive and Negative Symptom Scale ratings compared with baseline. Furthermore, 6 weeks of DHEA treatment was associated with significant improvement in cognitive functions of visual sustained attention and visual and movement skills compared with placebo conditions. The DHEA augmentation was associated with elevations of serum concentrations of both DHEA and its sulfate ester. The DHEA treatment was well tolerated without any serious adverse effects.\n This short-term study does not support DHEA's value as an effective adjunct in the treatment of symptoms, side effects, and quality-of-life impairment in schizophrenia, while suggesting that DHEA improves sustained attention and visual and movement skills. A long-term, large-scale study with a broader dose range is warranted to further investigate DHEA's role in the management of schizophrenia.", "To determine if dehydroepiandrosterone (DHEA) is beneficial in the treatment of systemic lupus erythematosus (SLE).\n In a double-blind, placebo-controlled, randomized trial, 28 female patients with mild to moderate SLE were given DHEA 200 mg/day or placebo for 3 months. Outcomes included the SLE Disease Activity Index (SLEDAI) score, patient's and physician's overall assessments of disease activity, and concurrent corticosteroid dosages (which were adjusted as clinically indicated).\n In the patients who were receiving DHEA, the SLEDAI score, patient's and physician's overall assessment of disease activity, and concurrent prednisone dosage decreased, while in the patients taking placebo, small increases were seen. The difference in patient's assessment between the groups was statistically significant (P = 0.022, adjusted). Lupus flares occurred more frequently in the placebo group (P = 0.053). Mild acne was a frequent side effect of DHEA.\n DHEA may be useful as a therapeutic agent for the treatment of mild to moderate SLE. Further studies of DHEA in the treatment of SLE are warranted.", "The objective of this study was to evaluate the efficacy of low dose dehydroepiandrosterone (DHEA) on health-related quality of life (HRQOL) in glucocorticoid treated female patients with systemic lupus erythematosus (SLE). Forty one women ( >or= 5 mg prednisolone/day) were included in a double-blind, randomized, placebo-controlled study for 6 months where DHEA was given at 30 mg/20 mg ( <or= 45/ >or= 46 years) daily, or placebo, followed by 6 months open DHEA treatment to all patients. HRQOL was assessed at baseline, 6 and 12 months, using four validated questionnaires and the patients' partners completed a questionnaire assessing mood and behaviour at 6 months. DHEA treatment increased serum levels of sulphated DHEA from subnormal to normal. The DHEA group improved in SF-36 \"role emotional\" and HSCL-56 total score (both p<0.05). During open DHEA treatment, the former placebo group improved in SF-36 \"mental health\" (p<0.05) with a tendency for improvement in HSCL-56 total score (p=0.10). Both groups improved in McCoy's Sex Scale during active treatment (p<0.05). DHEA replacement decreased high-density lipoprotein (HDL) cholesterol and increased insulin-like growth factor I (IGF-I) and haematocrit. There were no effects on bone density or disease activity and no serious adverse events. Side effects were mild. We conclude that low dose DHEA treatment improves HRQOL with regard to mental well-being and sexuality and can be offered to women with SLE where mental distress and/or impaired sexuality constitutes a problem.", "To evaluate the effects of combination estrogen/androgen therapy on muscle mass, strength and endurance, serum hormone and lipid profiles, and quality of life measures in postmenopausal women.\n Prospective, randomized, placebo-controlled pilot study at a tertiary care medical center. Fifty postmenopausal women were randomized to a 12-week course of (1) dehydroepiandrostenedione (DHEA) 50 mg daily, (2) conjugated equine estrogen (CEE) 0.625 mg daily, (3) DHEA 50 mg+CEE 0.625 mg daily, or (4) placebo. Main outcome measures of lower extremity muscle (calf) mass, functional muscle parameters, serum hormone and lipid levels, and quality of life (QOL) were obtained at baseline and after treatment. Statistical analysis compared percent change from baseline values and treatment differences among outcomes.\n Significant increases in mean DHEA, DHEA sulfate (DHEA-S), testosterone, and androstenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo. Compared with no hormone therapy, none of the supplemental hormone groups caused significant changes in muscle mass, muscle strength, muscle endurance, feelings of well-being, sleep, or sexual function.\n Androgen replacement therapy, with DHEA, to menopausal women increases serum androgen levels without any appreciable effect on muscle cross-sectional area, muscle strength, muscle function, or improvement in health-related QOL.", "Because dehydroepiandrosterone (DHEA) is an adrenal steroid hormone with weak intrinsic androgenic properties that can be converted in peripheral tissues into more potent sex hormones, one might expect a positive effect of DHEA on bone mineral density (BMD). We evaluated the effects on lumbar BMD of oral DHEA, 200 mg/day, for 1 year in female patients with quiescent systemic lupus erythematosus (SLE).\n The study subjects were 60 women with SLE. All participants gave informed consent to participate in a double-blind, placebo-controlled study on the effects of DHEA on fatigue and general well-being. BMD was measured with dual-energy x-ray absorptiometry (DEXA) at baseline and after 12 months.\n Fifty-eight patients (mean age 42.6 years) could be evaluated; 2 patients (both in the DHEA group) refused to undergo DEXA a second time. In premenopausal women, DHEA did not influence BMD significantly. There was a significant increase in BMD with use of DHEA in postmenopausal women who were not receiving bisphosphonates or estrogen-containing medications. This increase was not observed in the group receiving placebo.\n In premenopausal women with quiescent SLE, use of DHEA does not have a significant effect on BMD. DHEA may increase BMD in postmenopausal SLE patients if they are not already protected from bone loss by use of estrogens or bisphosphonates. Small numbers, due to the absence of stratification for menopausal status, and the use of antiresorptive agents at randomization preclude firmer conclusions based on the results of this study.", "To examine the effects of dehydroepiandrosterone (DHEA) supplementation on cognitive function and quality of life in healthy older adults.\n Double-blind, randomized, controlled clinical trial.\n Clinical research facility.\n One hundred ten men and 115 women aged 55 to 85 (mean +/- standard deviation 68 +/- 8).\n Fifty milligrams daily oral DHEA versus placebo for 1 year.\n Six cognitive function tests at baseline and 12 months, the Beck Depression Inventory (BDI), the Medical Outcomes Study 36-item Short Form Survey (SF-36), the Life Satisfaction Index-Z, the Satisfaction with Life Scale, the Female Sexual Function Index (in women), and the 15-item International Index of Erectile Function (in men) at baseline and 3, 6, and 12 months.\n There were no differences between the DHEA and placebo groups in change over time in cognitive function (P>.10). Over time, BDI scores decreased for men (P=.006) and women (P=.02), and Satisfaction with Life Scale scores increased for women (P=.004), but there were no differences between the DHEA and placebo groups over time on these measures or the SF-36, Life Satisfaction Index-Z scale, or sexual function scales (P>.10).\n DHEA supplementation has no benefit on cognitive performance or well-being in healthy older adults, and it should not be recommended for that purpose in the general population.", "Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown.\n We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life.\n As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter (9.2 micromol per liter) in men and by 3.8 microg per milliliter (10.3 micromol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects.\n Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society." ]

[ "15321573", "15177859", "7566849", "11641687", "8238138", "9316951", "3822279", "9423752", "9855591" ]

[ "Upright versus recumbent position in the second stage of labour in women with combined spinal-epidural analgesia.", "A prospective randomised trial on the effect of position in the passive second stage of labour on birth outcome in nulliparous women using epidural analgesia.", "Randomized trial of epidural versus intravenous analgesia during labor.", "A randomized trial of labor analgesia in women with pregnancy-induced hypertension.", "The effect of intrapartum epidural analgesia on nulliparous labor: a randomized, controlled, prospective trial.", "Cesarean delivery: a randomized trial of epidural versus patient-controlled meperidine analgesia during labor.", "Continuous infusion epidural analgesia with lidocaine: efficacy and influence during the second stage of labor.", "Nulliparous active labor, epidural analgesia, and cesarean delivery for dystocia.", "The influence of epidural analgesia on cesarean delivery rates: a randomized, prospective clinical trial." ]

[ "Neuraxial blockade is widely used for pain relief in labour. This form of analgesia may be associated with an increase in instrumental delivery rates due to dystocia. 'Traditional' epidurals cause motor blockade and hence immobility. Using a low dose anaesthetic-opioid combination with either epidural or combined spinal-epidural, selective sensory blockade can be achieved, allowing mobility as well as pain relief. In this study, we randomised women with combined spinal-epidural analgesia either to mobilise (upright group n = 25) or to remain recumbent (n = 41) in the second stage of labour. We found women in the upright group had significantly shorter total second stage, (132 vs 109 min,P = 0.019) particularly during the pushing phase (73 vs 51 min, P = 0.011). Although there were fewer instrumental deliveries in the upright group, this was not statistically significant. Women who were randomised to the upright group, did actually mobilise. We conclude that mobilisation in the second stage of labour is possible, and may reduce the length of the second stage.", "To determine whether the rate of instrumental birth in nulliparous women using epidural analgesia is affected by maternal position in the passive second stage of labour.\n A pragmatic prospective randomised trial.\n Consultant maternity unit in the Midlands.\n One hundred and seven nulliparous women using epidural analgesia and reaching the second stage of labour with no contraindications to spontaneous birth.\n The lateral versus the supported sitting position during the passive second stage of labour.\n Mode of birth, incidence of episiotomy, and perineal suturing.\n Recruitment was lower than anticipated (107 vs. 220 planned). Lateral position was associated with lower rates of instrumental birth rate (lateral group 33%; sitting group 52%; p=0.05, RR 0.64, CI for RR: 0.40-1.01; Number-needed-to-treat (NNT)=5), of episiotomy (45% vs. 64%; p=0.05, RR 0.66, CI for RR: 0.44-1.00, NNT=5), and of perineal suturing (78% vs. 86%; p=0.243, RR 0.75, CI for RR 0.47-1.17). The odds ratio for instrumental birth in the sitting group was 2.2 (CI 1.00-4.6). Logistic regression of potential confounder variables was undertaken, due to a large variation in maternal weight between the randomised groups. Of the nine possible confounders tested, only position of the baby's head at full dilation affected the risk of instrumental birth significantly (p=0.4, OR 2.7 where the fetal head was in the lateral or posterior position). Maternal weight did not appear to have any effect. The odds ratio for instrumental delivery for women randomised to the sitting position was slightly higher within the logistic regression model (adjusted OR 2.3).\n Women randomised to the lateral position had a better chance of a spontaneous vaginal birth than those randomised to the supported sitting position. Position of the babies head at full dilation had an additional effect on mode of birth. These effects are not conclusively generalizable. RECOMMENDATIONS FOR PRACTICE: The lateral position is likely to be at best beneficial, and at the worst no less harmful than the sitting position for most women and their babies who meet the criteria set for this study. Conclusive evidence for or against the technique should be established using larger trials.", "To compare the effects of epidural analgesia with intravenous (IV) analgesia on the outcome of labor.\n Thirteen hundred thirty women with uncomplicated term pregnancies and in spontaneous labor were randomized to be offered epidural bupivacaine-fentanyl or IV meperidine analgesia during labor.\n Comparison of the allocation groups by intent to treat revealed a significant association between epidural allocation and operative delivery for dystocia. However, only 65% of each randomization group accepted the allocated treatment. Four hundred thirty-seven women accepted and received meperidine as allocated, and they were compared with 432 women accepting epidural allocation. Significant associations resulted between epidural administration and prolongation of labor, increased rate of oxytocin administration, chorioamnionitis, low forceps, and cesarean delivery. Because of the high rate of noncompliance with treatment allocation, a multifactorial regression analysis was performed on the entire cohort, and a twofold relative risk of cesarean delivery persisted in association with epidural treatment. The impact of epidural treatment on cesarean delivery was significant for both nulliparous and parous women (risk ratios 2.55 and 3.81, respectively). Epidural analgesia provided significantly better pain relief in labor than did parenteral meperidine.\n Although labor epidural analgesia is superior to meperidine for pain relief, labor is prolonged, uterine infection is increased, and the number of operative deliveries are increased. A two- to fourfold increased risk of cesarean delivery is associated with epidural treatment in both nulliparous and parous women.", "The purpose of this study was to compare the peripartum and perinatal effects of epidural with intravenous labor analgesia in women with pregnancy-induced hypertension.\n Women with pregnancy-induced hypertension who had consented to participate were randomized to receive either epidural or intravenous analgesia for labor pain. Both methods were given according to standardized protocols. All women received magnesium sulfate seizure prophylaxis. Obstetric and neonatal outcomes were compared according to intent-to-treat allocation.\n Seven hundred thirty-eight women were randomized: 372 women were given epidural analgesia, and 366 women were given intravenous analgesia. Maternal characteristics were similar, including the severity of hypertension. Epidural analgesia was associated with a significantly prolonged second-stage labor, an increase in forceps deliveries, and an increase in chorioamnionitis. Cesarean delivery rates and neonatal outcomes were similar. Pain relief was superior with the epidural method. Hypotension required treatment in 11% of women in the epidural group.\n Epidural labor analgesia provides superior pain relief but no additional therapeutic benefit to women with pregnancy-induced hypertension.", "Our purpose was to determine the effect of epidural analgesia on nulliparous labor and delivery.\n Normal term nulliparous women in early spontaneous labor were randomized to receive either narcotic or epidural analgesia.\n When compared with the group receiving narcotic analgesia (n = 45), the group receiving epidural analgesia (n = 48) had a significant prolongation in the first and second stages of labor, an increased requirement for oxytocin augmentation, and a significant slowing in the rate of cervical dilatation. Epidural analgesia was associated with a significant increase in malposition (4.4% vs 18.8%, p < 0.05). Cesarean delivery occurred more frequently in the epidural group (2.2% vs 25%, p < 0.05), primarily related to an increase in cesarean section for dystocia (2.2% vs 16.7%, p < 0.05).\n In a randomized, controlled, prospective trial epidural analgesia resulted in a significant prolongation in the first and second stages of labor and a significant increase in the frequency of cesarean delivery, primarily related to dystocia.", "Reports indicate that the administration of epidural analgesia for pain relief during labor interferes with labor and increases cesarean deliveries. However, only a few controlled trials have assessed the effect of epidural analgesia on the incidence of cesarean delivery. The authors' primary purpose in this randomized study was to evaluate the effects of epidural analgesia on the rate of cesarean deliveries by providing a suitable alternative: patient-controlled intravenous analgesia.\n Seven hundred fifteen women of mixed parity in spontaneous labor at full term were randomly assigned to receive either epidural analgesia or patient-controlled intravenous meperidine analgesia. Epidural analgesia was maintained with a continuous epidural infusion of 0.125% bupivacaine with 2 microg/ml fentanyl. Patient-controlled analgesia was maintained with 10-15 mg meperidine given every 10 min as needed using a patient-controlled pump. Procedures recorded in a manual that prescribed the intrapartum management were followed for each woman randomized in the study.\n A total of 358 women were randomized to receive epidural analgesia, and 243 (68%) of these women complied with the epidural analgesia protocol. Similarly, 357 women were randomized to receive patient-controlled intravenous meperidine analgesia, and 259 (73%) of these women complied with the patient-controlled intravenous analgesia protocol. Only five women who were randomized and received patient-controlled intravenous meperidine analgesia according to the protocol crossed over to epidural analgesia due to inadequate pain relief. There was no difference in the rate of cesarean deliveries between the two analgesia groups using intention-to-treat analysis based on the original randomization (epidural analgesia, 4% [95% CI: 1.9-6.2%] compared with patient-controlled intravenous analgesia, 5% [95% CI: 2.6-7.2%]). Similar results were observed for the analysis of the protocol-compliant groups (epidural analgesia, 5% [95% CI: 2.6-8.5%] compared with patient-controlled intravenous analgesia, 6% [95% CI: 3-8.9%]). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received patient-controlled intravenous analgesia.\n Epidural analgesia was not associated with increased numbers of cesarean delivery when compared with a suitable alternative method of analgesia.", "A randomized double-blind study evaluated the analgesic efficacy and influence of maintaining a continuous epidural infusion of 0.75% lidocaine during the second stage of labor in nulliparous women. When the cervix was 8 cm or more dilated, unidentified study solution was substituted for the known 0.75% lidocaine solution and continued until delivery. The study solution for 26 patients was 0.75% lidocaine; 27 subjects received saline. During the first stage of labor, 88% of women in the lidocaine group and 81% of women in the saline group had analgesia of excellent or good quality, a nonsignificant difference. During the second stage, there was a tendency (not statistically significant) toward improved analgesia quality in the lidocaine patients, but there was no significant difference in the frequency of perineal anesthesia (23% lidocaine, 7% saline). There was no difference between the groups in the duration of the second stage of labor (73 +/- 63 versus 76 +/- 48 minutes). Operative delivery frequency was similar (31 and 37%), as were umbilical cord blood acid-base values. It is concluded that maintenance of the continuous epidural infusion of 0.75% lidocaine did not prolong the second stage of labor, but it also did not significantly differ from saline in quality of second stage analgesia or frequency of perineal anesthesia.", "Our purpose was to examine the effect of epidural analgesia on dystocia-related cesarean delivery in actively laboring nulliparous women.\n Active labor was confirmed in nulliparous women by uterine contractions, cervical dilatation of 4 cm, effacement of 80%, and fetopelvic engagement. Patients were randomized to one of two groups: epidural analgesia or narcotics. A strict protocol for labor management was in place. Patients recorded the level of pain at randomization and at hourly intervals on a visual analog scale. Elective outlet operative vaginal delivery was permitted.\n One hundred women were randomized. No difference in the rate of cesarean delivery for dystocia was noted between the groups (epidural 8%, narcotic 6%; p = 0.71). No significant differences were noted in the lengths of the first (p = 0.54) or second (p = 0.55) stages of labor or in any other time variable. Women with epidural analgesia underwent operative vaginal delivery more frequently (p = 0.004). Pain scores were equivalent at randomization, but large differences existed at each hour thereafter. The number of patients randomized did not achieve prestudy estimates. A planned interim analysis of the results demonstrated that we were unlikely to find a statistically significant difference in cesarean delivery rates in a trial of reasonable duration.\n With strict criteria for the diagnosis of labor and with use of a rigid protocol for labor management, there was no increase in dystocia-related cesarean delivery with epidural analgesia.", "The effects of epidural analgesia on the progress of labor are controversial. The objective of this study was to determine the effect of epidural analgesia on cesarean delivery rates in a population of patients randomly assigned to receive either epidural analgesia or intravenous opioids for intrapartum pain relief.\n From January 1995 to May 1996, 318 spontaneously laboring, term, nulliparous patients were randomly assigned to receive either intravenous opioids or epidural analgesia for pain relief. Labor was managed according to the principles of active management of labor. Cesarean delivery was performed for obstetric indications. Data analysis was conducted on an intent-to-treat basis. A subanalysis was subsequently performed on patients who were compliant with the allocated form of treatment.\n One hundred sixty-two patients were randomly assigned to receive intravenous meperidine and 156 were randomly assigned to receive epidural analgesia. Maternal age, gravidity, race, gestational age, and cervical dilatation at admission and at first analgesic dose did not differ between the groups. Intent-to-treat data analysis revealed no significant difference in the cesarean delivery rate between the 2 groups, being 13.6% in the opioid group and 9.6% in the epidural group (relative risk 0.70, 95% confidence interval 0.38-1.31, P >.05). Cesarean delivery rates for the indication of dystocia also did not differ, being 10.5% in the opioid group and 5.8% in the epidural group (relative risk 0.56, 95% confidence interval 0.26-1.21, P >.05). Subanalysis of the data from patients who were compliant with the allocated form of treatment revealed that patients in the epidural group (n = 147) were 3 times more likely to have an active phase duration >/=8 hours and were 10 times more likely to require >/=2 hours in the second stage of labor than were those in the opioid group (n = 78). There were no significant differences in cesarean delivery rates in this subanalysis, being 7.7% in the opioid group and 8.8% in the epidural group (relative risk 1.15, 95% confidence interval 0.45-2.91, P >. 05). The cesarean delivery rates for dystocia were also similar in the subanalysis, being 3.8% in the opioid group and 5.5% in the epidural group (relative risk 1.42, 95% confidence interval 0.39-5. 22, P >.05).\n Epidural analgesia provides safe and effective intrapartum pain control and may be administered without undesirable effects on labor outcome." ]

[ "11192954", "9926148", "10974183", "8620707", "9112877", "12953145", "10767227", "16327534", "19075206" ]

[ "Home-based exercise is capable of preserving hospital-based improvements in severe chronic obstructive pulmonary disease.", "Exercise training improves recovery in patients with COPD after an acute exacerbation.", "Short- and long-term effects of outpatient rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial.", "A comparison between an outpatient hospital-based pulmonary rehabilitation program and a home-care pulmonary rehabilitation program in patients with COPD. A follow-up of 18 months.", "Hospital vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease.", "Long-term effects of a maintenance program after supervised or self-monitored training programs in patients with COPD.", "Long-term effects of outpatient rehabilitation of COPD: A randomized trial.", "Managing chronic obstructive pulmonary disease in the community. A randomized controlled trial of home-based pulmonary rehabilitation for elderly housebound patients.", "Effects of home-based pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial." ]

[ "We examined the feasibility of home-based walking training to maintain the benefits of a short-term exercise training in patients with severe chronic obstructive pulmonary disease (COPD). After initial recovery from an exacerbation, 46 patients were randomized into a training and a control group, and 30 patients completed the programme (mean +/- SD FEV1, 36 +/- 7% predicted). The training group performed a 10-day walking training programme in the hospital, followed by a 6-month programme of supervised walking training at home, integrated into daily activities. The control group did not have exercise training in the hospital or at home. Until 6 months after discharge, lung function, exercise performance and symptom scores were assessed. Six-minute walking distance in the training group improved from day 1 to day 10 (P<0.001) and this effect was maintained over 6 months (P<0.001). On average, daily walking distance at home was 2308 m and walking was reported on 157 days. Quality of life (QoL) scores changed significantly over 6 months (P<0.001). The control group showed no significant changes in exercise performance or QoL scores throughout the whole study period. Therefore, (i) significant improvements in exercise performance and Chronic Respiratory Disease Questionnaire (CRQ) scores could be achieved after recovery from an exacerbation and (ii) these improvements were maintained after discharge, when supported by a home-based walking training.", "Clinical experience suggests that exercise is beneficial for recovery after an acute exacerbation in patients with severe chronic obstructive pulmonary disease (COPD). The aim of this study was to quantify the clinical benefit of exercise in these patients. Twenty-nine inpatients were randomly assigned to a training group (n = 15, FEV1 34% pred) or a control group (n = 14, FEV1 38% pred). On ten consecutive days, patients in the training group performed a 6-min treadmill walking test and, in addition, five walking sessions per day at > or = 75% of the respective treadmill walking distance. Patients in the control group performed only treadmill walking tests on days 1, 5, and 10. To directly compare the possible benefit of exercise training all patients had an exercise test on day 11 at the same work load as on day 1. In the training group, 6-min walking distance increased from 237 to 420 m, in the control group from 230 to 255 m over the 10 day period which was significantly different (P < 0.0001). Minute ventilation and oxygen uptake increased significantly (P < 0.05) in the training but not in the control group. When comparing exercise tests on days 1 and 11, minute ventilation, oxygen uptake, PaCO2, lactic acid concentration, and Borg scale were significantly reduced to achieve the same work load (P < 0.01) only in the training group. Intrathoracic gas volume and residual volume decreased, and FEV1 and vital capacity increased in the training (P < 0.05) but not in the control group. Our data demonstrate that exercise training significantly improves the exercise capacity in patients with severe COPD after an acute exacerbation of their disease.", "Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease (COPD) in the short term, but their long-term effects are not known. We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD.\n One hundred patients were randomly assigned to receive either an exercise training program that included cycling, walking, and strength training (n = 50) or usual medical care (n = 50). Thirty-four patients in the training group were evaluated after 6 months (end of training), and 26 were evaluated after 18 months of follow-up. In the control group, 28 patients were evaluated at 6 months and 23 after 18 months. We measured pulmonary function, 6-minute walking distance, maximal exercise capacity, peripheral and respiratory muscle strength, and quality of life (on a 20 to 140-point scale), and estimated the cost-effectiveness of the program.\n At 6 months, the training group showed improvement in 6-minute walking distance [mean difference (training - control) of 52 m; 95% confidence interval (CI), 15 to 89 m], maximal work load (12 W; 95% CI, 6 to 19 W), maximal oxygen uptake (0.26 liters/min; 95% CI, 0.07 to 0.45 liters/min), quadriceps force (18 Nm; 95% CI, 7 to 29 Nm), inspiratory muscle force (11 cm H(2)O; 95% CI, 3 to 20 cm H(2)O), and quality of life (14 points; 95% CI, 6 to 21 points; all P <0.05). At 18 months all these differences persisted (P <0.05), except for inspiratory muscle strength. For 6-minute walking distance and quality of life, the differences between the training group and controls at 18 months exceeded the minimal clinically-important difference.\n Among patients who completed the 6-month program, outpatient training resulted in significant and clinically relevant changes in 6-minute walking distance, maximal exercise performance, peripheral and respiratory muscle strength, and quality of life. Most of these effects persisted 18 months after starting the program.", "In this study, the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program (HRP) are compared with those of a 12-week home-care rehabilitation program (HCRP) in COPD patients. A control group received no rehabilitation therapy.\n After randomization and stratification, effects on lung function, exercise performance (4-min walking test and cycle ergometer test), dyspnea, and leg effort during exercise, and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation (mean [SD] FEV1 percent predicted, 42.8 [8.4]).\n After HRP and HCRP, at 3 to 6 months after the start of the study, equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test. However, whereas after HRP at longer term values tended to return to baseline outcome, after HCRP a further ongoing significant improvement in exercise capacity was observed, while Borg dyspnea scores remained significantly improved over 18 months. Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP. Lung function, arterial oxygen saturation, and heart frequency during exercise did not change. A significant improvement in well-being was maintained over 18 months in both rehabilitation groups.\n Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation. Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting.", "Supervised, hospital-based exercise rehabilitation programs are effective for improving functional status for patients with claudication due to peripheral arterial occlusive disease. However, it has been suggested that unsupervised, home-based exercise programs, which have been relatively little evaluated, would be equally efficacious as compared with hospital-based programs. The authors tested the hypothesis that a hospital-based exercise rehabilitation program would improve treadmill exercise performance more than a home-based program. Of 20 consecutively enrolled patients with claudication, 10 were randomly placed into a supervised, hospital-based program and 10 into an unsupervised, home-based program for a three-month period. Exercise performance was evaluated by treadmill testing using a graded protocol. In addition, functional status was evaluated by the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study SF-20 questionnaire (MOS). Patients in the hospital-based program were treated with treadmill walking three times a week for one hour/visit. Patients in the home-based program were instructed to walk at least three times a week and were contacted weekly to provide encouragement and to record compliance with the program. Patients in the hospital-based group improved peak walking time by 137%, pain-free walking time by 150%, and peak oxygen consumption by 19% (all P < 0.05). Patients reported an improved walking distance and speed according to WIQ data (both P < 0.05). In addition, the MOS physical functioning score in the hospital-based group improved by 20 percentage points (P < 0.05). In contrast, patients in the home-based program did not improve exercise performance measured on the treadmill. Improvement in the ability to walk on the treadmill was greater in the hospital-based than the home-based program (P < 0.05). The ability to walk distances was the only questionnaire measure that improved in persons who received the home-based program (P < 0.05). Preliminary results suggest that a supervised, hospital-based program is more effective for improving treadmill exercise performance than an unsupervised, home-based program.", "The evaluation of a 13-month maintenance program (MP) for 39 severe COPD patients with FEV(1)%pred 44(7)% who, as result of two different 8-week leg exercise training (LET) programs, one supervised at the hospital (group S; n = 20) and the other self-monitored (SM; n = 19), had achieved different levels of exercise tolerance. After LET, patients in group S had a higher maximal oxygen uptake and endurance time than patients in the SM group [ O(2)max 1.43(0.30) l. min(-1)] vs l.25(0.27) l. min(-1) and endurance-time 16(4) min vs 12 (5) min, respectively). During the MP patients were advised to walk vigorously at least 4 km/day, 4 times/wk. After the MP, while endurance time remained higher than at baseline, it had decreased ( p < 0.01) immediately after LET in both groups and no differences were evident between groups (11(4) min and 10(4), respectively). In contrast, Chronic Respiratory Diseases Questionnaire scores, which had improved significantly after LET in both groups, remained high. Long-term effects of MP were independent of the training strategy or whether physiological improvements had been obtained with the initial LET. SM exercise programs do not seem capable of maintaining physiological improvements in exercise tolerance, though \"quality of life\" can be maintained.", "To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea, exercise, health-related quality of life, and hospitalization rate.\n Secondary-care respiratory clinic in Barcelona.\n We conducted a randomized controlled trial with blinding of outcome assessment and follow-up at 3, 6, 9, 12, 18, and 24 months. Sixty patients with moderate to severe COPD (age 65 +/- 7 years; FEV(1) 35 +/- 14%) were recruited. Thirty patients randomized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy, 3 months of daily supervised exercise, and 6 months of weekly supervised breathing exercises. Thirty patients randomized to the control group received standard care.\n We found significant differences between groups in perception of dyspnea (p < 0.0001), in 6-min walking test distance (p < 0.0001), and in day-to-day dyspnea, fatigue, and emotional function measured by the Chronic Respiratory Questionnaire (p < 0. 01). The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up. The PR group experienced a significant (p < 0.0001) reduction in exacerbations, but not the number of hospitalizations. The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three.\n Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years.", "Pulmonary rehabilitation is essential for managing chronic obstructive pulmonary disease (COPD). Housebound COPD patients are frequently excluded from this treatment because they are unable to access outpatient pulmonary rehabilitation programs because of the severity of their disease. This randomized controlled trial assesses the effects of a 12-week home-based pulmonary rehabilitation program for 60 housebound COPD patients older than 60 years.\n Intervention patients received an individually tailored supervised walking and arm exercise program as well as individual multidisciplinary education sessions on COPD and its management. Outcomes were assessed using the 6-minute walk test, St George's respiratory questionnaire, and Borg score of perceived breathlessness. Healthcare utilization was assessed using hospital admission rates with exacerbation of COPD and average length of stay at readmission.\n Complete data for 23 patients in each group were available for analysis. There was no significant difference between groups on baseline measures. Compared with the control group, intervention patients demonstrated a significant improvement in 6-minute walk test (P = .023), Borg score of perceived breathlessness (P = .024), St George's respiratory questionnaire total score (P = .020), and impact subscore (P = .024). At 6 months, the intervention group had a significantly shorter average length of stay at readmission to hospital with exacerbation (P = .035).\n A 12-week home-based pulmonary rehabilitation is effective in improving exercise tolerance, perception of breathlessness, and quality of life for housebound COPD patients. To manage COPD in the community more effectively, health services should focus on expanding home-based pulmonary rehabilitation.", "Home-based rehabilitation is a promising approach to improve access to pulmonary rehabilitation.\n To assess whether self-monitored, home-based rehabilitation is as effective as outpatient, hospital-based rehabilitation in patients with chronic obstructive pulmonary disease (COPD).\n Randomized, multicenter, noninferiority trial.\n 10 academic and community medical centers in Canada.\n 252 patients with moderate to severe COPD.\n After a 4-week education program, patients took part in home-based rehabilitation or outpatient, hospital-based rehabilitation for 8 weeks. They were followed for 40 weeks to complete the 1-year study.\n The primary outcome was the change in Chronic Respiratory Questionnaire dyspnea subscale score at 1 year. The primary analysis took a modified intention-to-treat approach by using all patients who provided data at the specified follow-up time, regardless of their level of adherence. The analysis used regression modeling that adjusted for the effects of center, sex, and baseline level. All differences were computed as home intervention minus outpatient intervention.\n Both interventions produced similar improvements in the Chronic Respiratory Questionnaire dyspnea subscale at 1 year: improvement in dyspnea of 0.62 (95% CI, 0.43 to 0.80) units in the home intervention (n = 107) and 0.46 (CI, 0.28 to 0.64) units in the outpatient intervention (n = 109). The difference between the 2 treatments at 1 year was small and clinically unimportant. The 95% CI of the difference did not exceed the prespecified noninferiority margin of 0.5: difference in dyspnea score of 0.16 (CI, -0.08 to 0.40). Most adverse events were related to COPD exacerbations. No serious adverse event was considered to be related to the study intervention.\n The contribution of the educational program to the improvement in health status and exercise tolerance cannot be ascertained.\n Home rehabilitation is a useful, equivalent alternative to outpatient rehabilitation in patients with COPD." ]

[ "12145577", "16041208", "9449869", "19577251", "2039294", "1739177", "20232173", "18202889", "14607696" ]

[ "Laparoscopic common bile duct exploration and cholecystectomy versus endoscopic stone extraction and laparoscopic cholecystectomy for choledocholithiasis. A prospective randomized study.", "Postoperative ERCP versus laparoscopic choledochotomy for clearance of selected bile duct calculi: a randomized trial.", "Randomised trial of laparoscopic exploration of common bile duct versus postoperative endoscopic retrograde cholangiography for common bile duct stones.", "Laparoscopic exploration of common bile duct with primary closure versus T-tube drainage: a randomized clinical trial.", "Choledocholithiasis. Endoscopic sphincterotomy or common bile duct exploration.", "Precholecystectomy endoscopic cholangiography and stone removal is not superior to cholecystectomy, cholangiography, and common duct exploration.", "Is the use of T-tube necessary after laparoscopic choledochotomy?", "A randomized comparison of primary closure and T-tube drainage of the common bile duct after laparoscopic choledochotomy.", "Duodenoscopy in treatment of acute gallstone pancreatitis." ]

[ "Our objective is to compare the results of laparoscopic cholecystectomy (LC) and common bile duct (CBD) exploration to those of endoscopic stone extraction and LC in patients with CBD lithiasis based on a prospective randomized study.\n From April 1997 until August 2000, 78 patients were assigned in two groups. Group A (n'36) patients underwent laparoscopic either direct or trancystic duct, CBD exploration and LC. Group B (n'42) patients were referred for endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) for duct clearance and at a later stage LC was performed. Selection of patients of both groups was done, considering prognostic factors of a preliminary study.\n Laparoscopic duct clearance was achieved in 85.7% of patients while the respective percentage for the combined approach was 84.3%.\n Laparoscopic CBD exploration is not yet established as the gold standard procedure for choledocholithiasis and there is the need for further randomized trials and possibly future meta-analyses.", "Prospectively evaluate whether for patients having laparoscopic cholecystectomy with failed trans-cystic duct clearance of bile duct (BD) stones they should have laparoscopic choledochotomy or postoperative endoscopic retrograde cholangiography (ERCP).\n Clinical management of BD stones found at laparoscopic cholecystectomy in the last decade has focused on pre-cholecystectomy detection with ERCP clearance in those with suspected stones. This clinical algorithm successfully clears the stones in most patients, but no stones are found in 20% to 60% of patients and rare unpredictably severe ERCP morbidity can result in this group. Our initial experience of 300 consecutive patients with fluoroscopic cholangiography and intraoperative clearance demonstrated that, for the pattern of stone disease we see, 66% of patients' BD stones can be cleared via the cystic duct with dramatic reduction in morbidity compared to the 33% requiring choledochotomy or ERCP. Given the limitations of the preoperative approach to BD stone clearance, this trial was designed to explore the limitations, for patients failing laparoscopic trans-cystic clearance, of laparoscopic choledochotomy or postoperative ERCP.\n Across 7 metropolitan hospitals after failed trans-cystic duct clearance, patients were intraoperatively randomized to have either laparoscopic choledochotomy or postoperative ERCP. Exclusion criteria were: ERCP prior to referral for cholecystectomy, severe cholangitis or pancreatitis requiring immediate ERCP drainage, common BD diameter of less than 7 mm diameter, or if bilio-enteric drainage was required in addition to stone clearance. Drain decompression of the cleared BD was used in the presence of cholangitis, an edematous ampulla due to instrumentation or stone impaction and technical difficulties from local inflammation and fibrosis. The ERCP occurred prior to discharge from hospital. Mechanical and extracorporeal shockwave lithotripsy was available. Sphincter balloon dilation as an alternative to sphincterotomy to allow stone extraction was not used. Major endpoints for the trial were operative time, morbidity, retained stone rate, reoperation rate, and hospital stay.\n From June 1998 to February 2003, 372 patients with BD stones had successful trans-cystic duct clearance of stones in 286, leaving 86 patients randomized into the trial. Total operative time was 10.9 minutes longer in the choledochotomy group (158.8 minutes), with slightly shorter hospital stay 6.4 days versus 7.7 days. Bile leak occurred in 14.6% of those having choledochotomy with similar rates of pancreatitis (7.3% versus 8.8%), retained stones (2.4% versus 4.4%), reoperation (7.3% versus 6.6%), and overall morbidity (17% versus 13%).\n These data suggest that the majority of secondary BD stones can be diagnosed at the time of cholecystectomy and cleared trans-cystically, with those failing having either choledochotomy or postoperative ERCP. However, because of the small trial size, a significant chance exists that small differences in outcome may exist. We would avoid choledochotomy in ducts less than 7 mm measured at the time of operative cholangiogram and severely inflamed friable tissues leading to a difficult dissection. We would advocate choledochotomy as a good choice for patients after Billroth 11 gastrectomy, failed ERCP access, or where long delays would occur for patient transfer to other locations for the ERCP.", "The management of stones in the common bile duct in the laparoscopic era is controversial. The three major options are preoperative endoscopic retrograde cholangiography (ERCP), laparoscopic exploration of the common bile duct (LECBD), or postoperative ERCP.\n Between August, 1995, and August, 1997, 471 laparoscopic cholecystectomies were done in our department. In 427 (91%), satisfactory peroperative cholangiography was obtained. In 80 (17%) of these cases there were stones in the common bile duct, 40 patients were randomised to LECBD and 40 to postoperative ERCP. If LECBD failed, patients had either open exploration of the common bile duct or postoperative ERCP. If one postoperative ERCP failed, the procedure was repeated until the common bile duct was cleared of stones or an endoprosthesis was placed to prevent stone impaction. The primary endpoints were duct-clearance rates, morbidity, operating time, and hospital stay. Analyses were by intention to treat.\n Age and sex distribution of patients was similar in the randomised groups. Duct clearance after the first intervention was 75% in both groups. By the end of treatment, duct clearance was 100% in the laparoscopic group compared with 93% in the ERCP group. Duration of treatment was a median of 90 min (range 25-310) in the laparoscopic group (including ERCPs for failed LECBD) compared with 105 min (range 60-255) in the postoperative ERCP group (p = 0.1, 95% CI for difference -5 to 40). Hospital stay was a median of 1 day (range 1-26) in the laparoscopic group compared with 3.5 days (range 1-11) in the ERCP group (p = 0.0001, 95% CI 1-2).\n LECBD is as effective as ERCP in clearing the common bile duct of stones. There is a non-significant trend to shorter time in the operating theatre and a significantly shorter hospital stay in patients treated by LECBD.", "Traditionally, the common bile duct (CBD) is closed with T-tube drainage after choledochotomy and removal of CBD stones. However, the insertion of a T-tube is not without complication and the patients have to carry it for several weeks before removal. In the laparoscopic era, surgery is performed with minimally invasive techniques in order to reduce the trauma, hasten recovery, and reduce the hospital stay of patients. T-tube insertion seems to negate these benefits. This randomized study was designed to compare the two methods applied after LCBDE and to determine whether primary closure can be as safe as closure with T-tube drainage.\n From May 2000 to January 2008, 93 consecutive patients with common bile duct stones (CBDS) and gallbladder in situ were enrolled in this randomized study to undergo laparoscopic cholecystectomy with laparoscopic common bile duct exploration (LCBDE). Intraoperative findings, postoperative complications, postoperative stay, and hospital expenses were recorded and analyzed.\n There was no mortality in both groups. A T-tube was inserted in 46 patients and the CBD was closed primarily in 47. There were no differences in the demographic characteristics or clinical presentations between the two groups. Compared with the T-tube group, the operative time and postoperative stay were significantly shorter, the hospital expenses were significantly lower, and the incidences of overall postoperative complications and biliary complications were statistically and insignificantly lower in the primary closure group.\n LCBDE with primary closure without external drainage after laparoscopic choledochotomy is feasible and as safe as T-tube insertion.", "A prospective randomized trial was conducted of preoperative endoscopic sphincterotomy and surgery (ES&S) or surgery alone (SA) in 52 patients with cholecystolithiasis and choledocholithiasis that were candidates for elective surgery. After ES&S 65% of patients were stone free. Eighty-eight per cent of patients with SA were stone free after surgery (p less than 0.05). Three patients in each group had residual stones at the completion of the operation. Five of these six had more than 20 common bile duct (CBD) stones. There was one episode of major hemorrhage in a patient in each group and no deaths. Costs were essentially equal for the individual patient with a successful ES as compared to SA. Societal costs of a program of preoperative endoscopic retrograde cholangiopancreatography and ES would be higher because of the cost of screening for patients with CBD stones. These results do not support preoperative ES as a technique for clearance of the CBD of stones on the basis of efficacy, morbidity rate, or cost.", "Thirty-four patients with suspected common bile duct stones were randomized to undergo endoscopic cholangiography and stone removal prior to open cholecystectomy or to have open cholecystectomy, operative cholangiography, and common bile duct exploration. Sixteen underwent the first protocol, and 18 the second. Analysis of the ability to clear stones from the common bile duct, morbidity, mortality, hospital stay, length of operation, and hospital cost showed no difference in outcome between patients treated by either method. These data suggest there is neither an advantage nor a disadvantage to treating patients with suspected duct stones by precholecystectomy endoscopic cholangiography and stone removal.", "Traditionally, the common bile duct (CBD) is closed with T-tube drainage after choledochotomy and removal of CBD stones. However, the insertion of a T-tube is not without complication.\n This randomized study was designed to compare the use of T-tube and primary closure of choledochotomy after laparoscopic choledochotomy to determine whether primary closure can be as safe as closure with T-tube drainage.\n Between February 2006 and June 2009, 122 consecutive patients with proven choledocholithiasis had laparoscopic choledochotomy. They were randomized into two equal groups: T-tube (n = 61) and primary closure (n = 61). Demographic data, intraoperative findings, postoperative complications, and postoperative stay were recorded.\n There was no mortality in both groups. There were no differences in the demographic characteristics or clinical presentations between the two groups. Compared with the T-tube group, the operative time and postoperative stay were significantly shorter and the incidences of overall postoperative complications and biliary complications were statistically and significantly lower in the primary closure group.\n Laparoscopic common bile duct exploration with primary closure without external drainage after laparoscopic choledochotomy is feasible, safe, and cost-effective. After verification of ductal clearance, the CBD could be closed primarily without T-tube insertion.", "Traditionally, the common bile duct (CBD) has been closed with T-tube drainage after laparoscopic choledochotomy and removal of CBD stones. However, insertion of the T-tube is related to some potential postoperative complications, and patients must carry the T-tube for several weeks before its removal. Primary closure of the CBD without drainage has been proposed as a safe alternative to T-tube placement after laparoscopic choledochotomy. This randomized study aimed to compare the postoperative course and final outcome between the two methods applied after LCBDE.\n Between January 2000 and January 2004, 80 patients treated with laparoscopic choledochotomy for CBD stones were randomly assigned to primary duct closure (n = 40) or T-tube drainage (n = 40). The primary end points were morbidity, operative time, postoperative stay, hospital expenses, and time until return to work.\n There were no differences in the demographic characteristics or clinical presentations between the two groups. In the primary closure group, the postoperative stay (5.2 +/- 2.2 vs 8.3 +/- 3.6 days) and the time until return to work (12.6 +/- 5.1 vs 20.4 +/- 13.2 days) were significantly shorter, the hospital expenses (8,638 +/- 2,946 vs 12,531 +/- 4,352 yuan) were significantly lower, and the incidences of postoperative complications (15% vs 27.5%) and biliary complications (10% vs 20%) were statistically and insignificantly lower than in the T-tube drainage group. In the primary closure group, six patients experienced postoperative complications, four of whom had biliary complications, compared, respectively, with 11 and 8 patients in the T-tube drainage group.\n This study showed that primary CBC closure after laparoscopic choledochotomy was a viable alternative to mandatory T-tube drainage.", "To probe the potential use of duodenoscopy in the diagnosis and treatment of acute gallstone pancreatitis (GP).\n Fourty-five patients with acute GP were randomly divided into endoscopic retrograde cholangiopancreatography (ERCP) group (n=20) and non-ERCP group (n=25). Each group was subdivided into mild and severe groups according to APACHE II scores. They were given supportive treatment combined with traditional Chinese medicine. The patients in the ERCP group received ERCP within 24 hours after admission. If there were stones in the common bile duct with stenosis of the inferior extremity or ampulla, endoscopic sphincterotomy (ES) was performed to extract the stones by basket. If no calculi were identified or multiple stones were large, endoscopic naso-biliary drainage (ENBD) was carried out.\n The incidence of complication, length of hospitalization and cost were markedly lower in patients with severe acute GP in the ERCP group than those in the non-ERCP group (P<0.05), in contrast to the 2 mild subgroups of the ERCP and non-ERCP groups (P>0.05).\n It is feasible, effective and safe to apply duodenoscopy in the treatment of severe acute GP." ]

[ "8970221", "10072411", "10864055", "12447954", "9870832", "2658574", "9792309", "18679151", "10197802" ]

[ "Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial.", "Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group.", "Use of amphotericin B colloidal dispersion in children.", "Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation.", "A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia.", "Empiric antifungal therapy in febrile granulocytopenic patients. EORTC International Antimicrobial Therapy Cooperative Group.", "Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections.", "Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial.", "Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo-controlled study." ]

[ "Fungal septicemia is a devastating disease in the neonate, especially in the low birth weight preterm infant who is especially vulnerable to disseminated fungal sepsis. The objective of this study was to compare the efficacy, safety and overall convenience of fluconazole vs. amphotericin B for the treatment of disseminated fungal sepsis in neonates.\n A prospective, randomized, collaborative study conducted at two South African neonatal units.\n Twenty-four infants with proven fungal septicemia were treated from June, 1992, to June, 1993. Twelve received fluconazole, 11 received amphotericin B and 1 was excluded. Assessment of hepatic, renal and hematologic functions were performed before, during and after treatment. The two groups were comparable at the time of enrollment into the study.\n Infants receiving amphotericin B had significantly higher values of total and direct bilirubin and alkaline phosphatase values at the end of treatment, while the fluconazole group showed a significant increase in the platelet count. The cumulative total numbers of days receiving intravenous therapy for the administration of antifungal drugs were 57 for the fluconazole group and 162 for the amphotericin group; no central lines were needed in the fluconazole group, whereas 3 babies given amphotericin B had central catheters for a cumulative total of 27 days. The case fatality rate was 33% in the fluconazole group and 45% in the amphotericin B group; there was still proof of fungal septicemia at the time of death in 1 patient given amphotericin B and 2 given fluconazole.\n Fluconazole showed fewer side effects than amphotericin B and was more convenient to use.", "In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity.\n We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy.\n The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P=0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P<0.001).\n Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity.", "To describe the experience with a new lipid-based amphotericin product (amphotericin B colloidal dispersion or ABCD) in children with fever and neutropenia who are at high risk for fungal infection.\n Forty-nine children with febrile neutropenia were treated in a prospective, randomized trial comparing ABCD with amphotericin B. An additional 70 children with presumed or proven fungal infection were treated with 5 different open-label studies of ABCD. Patients were registered into these studies for reasons of: 1) failure to respond to amphotericin B; 2) development of nephrotoxicity or preexisting renal impairment; or 3) willingness to participate in a dose-escalation study. Extensive data detailing response and toxicity were collected from each patient.\n In the randomized trial, there was significantly less renal toxicity in the children receiving ABCD than in those receiving amphotericin B (12.0% vs. 52.4% [P = 0.003]). Other adverse symptoms were not significantly different. In the additional open-label studies, although 80% of patients receiving ABCD reported some adverse symptom, the majority of these were infusion related, and nephrotoxicity was reported in only 12% of these patients.\n ABCD was well-tolerated at doses up to 5 times greater then those usually tolerated with amphotericin B. Renal toxicity was markedly less than expected, and there were no other unexpected severe toxicities. Further randomized studies are needed to further define the role of this and other liposomal products in children.", "Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation.\n Copyright 2002 Wiley-Liss, Inc.", "Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated.\n We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection.\n Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia.\n These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.", "The optimal management of fever in granulocytopenic patients remains controversial. Invasive fungal infections are common and life-threatening but are difficult to diagnose early. In this randomized study, we investigated the potential value of empiric administration of amphotericin B (versus no empiric antifungal therapy) in 132 patients remaining febrile and granulocytopenic despite broad-spectrum antibiotic therapy for four days.\n The patients were divided into two groups: 68 who were randomly assigned to receive empiric amphotericin B, and 64 who were randomly assigned to continue only the protocol antibiotics that they were already receiving. Amphotericin B was administered intravenously as follows: every other day at a dose of 1.2 mg/kg body weight or daily at a dose of 0.6 mg/kg body weight. Clinical response was evaluated as success or failure, depending upon the febrile course after randomization.\n Based on the evolution of fever, the response rate was 69% in the group of patients receiving empiric amphotericin B and 53% for the other group (p = 0.09). There were six documented (four severe) fungal infections in 64 patients randomized not to receive the antifungal therapy as compared to only one fungemia among 68 patients treated empirically with amphotericin B (p = 0.1). No deaths due to fungal infection occurred among the patients receiving empiric amphotericin B compared to four in the other group (p = 0.05). However, this study did not demonstrate a difference in survival between the two groups of patients (with or without empiric amphotericin B). The benefit of empiric administration of amphotericin B was primarily observed in specific subgroups of patients, such as those who did not receive any antifungal prophylaxis (78% versus 45%, p = 0.04), those who were severely granulocytopenic (69% versus 46%, p = 0.06), febrile patients with a clinically documented infection (75% versus 41%, p = 0.03), and patients older than 15 years of age (67% versus 47%, p = 0.06).\n These data suggest a benefit for early amphotericin B treatment in granulocytopenic patients with continued fever despite antibiotic therapy.", "It has been suggested that a better outcome of neutropenia-associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used. We now report a randomized multicentre study comparing liposomal amphotericin B (AmBisome, 5 mg/kg/d) to amphotericin B deoxycholate (AmB, 1 mg/kg/d) in the treatment of these infections. Of 106 possible patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group (n = 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients (n = 34) treated with AmB (P=0.09); P=0.03 for complete responders. A favourable trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis (P=0.05 and P=0.096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P=0.03). More patients on AmB had a >100% increase of their baseline serum creatinine (P<0.001). The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.", "Invasive candidiasis is increasingly prevalent in premature infants and seriously ill children, and pediatric data on available antifungal therapies are lacking.\n We conducted a pediatric substudy as part of a double-blind, randomized, multinational trial to compare micafungin (2 mg/kg) with liposomal amphotericin B (3 mg/kg) as first-line treatment of invasive candidiasis. Treatment success was defined as clinical and mycologic response at the end of therapy. Statistical analyses were descriptive, as the sample size meant that the study was not powered for hypothesis testing.\n One hundred six patients were included in the intent-to-treat population; and 98 patients-48 patients in the micafungin group and 50 patients in the liposomal amphotericin B group-in the modified intent-to-treat population. Baseline characteristics were balanced between treatment groups. Overall, 57 patients were <2 years old including 19 patients who were premature at birth; and 41 patients were 2 to <16 years old. Most patients (91/98, 92.9%) had candidemia, and 7/98 (7.1%) patients had other forms of invasive candidiasis. Treatment success was observed for 35/48 (72.9%) patients treated with micafungin and 38/50 (76.0%) patients treated with liposomal amphotericin B. The difference in proportions adjusted for neutropenic status was -2.4% [95% CI: (-20.1 to 15.3)]. Efficacy findings were consistent, independent of the neutropenic status, the age of the patient, and whether the patient was premature at birth. Both treatments were well tolerated, but with a lower incidence of adverse events that led to discontinuation in the micafungin group (2/52, 3.8%) compared with the liposomal amphotericin B group (9/54, 16.7%) (P = 0.05, Fisher exact test).\n Micafungin seems to be similarly effective and as safe as liposomal amphotericin B for the treatment of invasive candidiasis in pediatric patients. (ClinicalTrials.gov number, NCT00106288).", "Liposomal amphotericin (AmBisome) 2 mg/kg three times weekly was compared with placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation (BMT) for haematological malignancies. Prophylaxis began on day 1 of chemotherapy and continued until neutrophils regenerated or infection was suspected. Of 161 evaluable patients, 74 received AmBisome and 87 received placebo. Proven fungal infections developed in no patients on AmBisome and in three on placebo (3.4%) (P = NS). Suspected fungal infections requiring intervention with systemic antifungal therapy (usually amphotericin B) occurred in 31 patients on AmBisome (42%) and in 40 on placebo (46%) (P = NS). Suspected deep-seated infections developed in 21 (28.3%) and 31 (35.6%) patients, respectively (P = NS). Time to develop a suspected or proven deep-seated infection showed a trend in favour of AmBisome (P = 0.11). Fifty patients had fungal colonisation (48 with Candida spp, two with Aspergillus spp) of at least one body site during prophylaxis; 15 patients while receiving AmBisome (20%) and 35 while on placebo (40%) (P < 0.01). Time to colonisation was significantly delayed in the group receiving AmBisome (P < 0.05). Treatment-related toxicity was modest and no additional toxicity was observed in patients receiving AmBisome. AmBisome 2 mg/kg three times weekly is safe and reduces fungal colonisation in patients receiving intensive chemotherapy or BMT. However, despite encouraging trends, prophylactic AmBisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy." ]

[ "16579803", "12173139", "20435345", "15699235", "1676467", "18595969", "8100345", "7901636", "10837300" ]

[ "Randomised trial of vitamin A supplementation in pregnant women in rural Malawi found to be anaemic on screening by HemoCue.", "Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi.", "Effect of vitamin A supplementation in women of reproductive age on maternal survival in Ghana (ObaapaVitA): a cluster-randomised, placebo-controlled trial.", "Effect of postpartum maternal or neonatal vitamin A supplementation on infant mortality among infants born to HIV-negative mothers in Zimbabwe.", "Efficacy of vitamin A in reducing preschool child mortality in Nepal.", "Newborn vitamin A supplementation reduced infant mortality in rural Bangladesh.", "Vitamin A supplementation in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality. Ghana VAST Study Team.", "Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia.", "Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal." ]

[ "To assess the effects of vitamin A supplementation in women with anaemia during pregnancy.\n Single-centre randomised controlled trial.\n Rural community in southern Malawi, central Africa.\n Seven hundred women with singleton pregnancies at 12-24 weeks measured by ultrasound scan and with haemoglobin <11.0 g/dl by HemoCue screening method. Analysis was by intention to treat. All received iron and folate, and sulphadoxine/pyrimethamine for antimalarial prophylaxis.\n Women were randomised to receive oral supplementation with daily 5000 or 10,000 iu vitamin A, or placebo.\n Anaemia, as assessed by Coulter counter, severe anaemia, iron status and indices of infection.\n Vitamin A deficiency was, in this rural population, less common than predicted. Vitamin A supplementation had no significant impact on anaemia, severe anaemia, iron status and indices of infection. Vitamin A stores were less likely to be depleted at the end of pregnancy in supplemented groups.\n Vitamin A supplementation programmes to reduce anaemia should not be implemented in similar antenatal populations in rural sub-Saharan Africa unless evidence emerges of positive benefit on substantive clinical outcomes. Introducing public health interventions of unknown benefit and with unclear biological mechanisms can divert scarce resources from clinical and social interventions more likely to impact maternal mortality.", "Vitamin A is essential for immunity and growth. A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia, low birth weight, growth failure, HIV transmission, and mortality. Women received daily doses of iron and folate, either alone or combined with vitamin A (3 mg retinol equivalent), from 18-28 weeks' gestation until delivery. In the vitamin A and control groups, respectively, the mean (+/-SE) birth weights were 2895+/-31 g and 2805+/-32 g (P=.05), the proportions of low-birth-weight infants were 14.0% and 21.1% (P=.03), the proportions of anemic infants at 6 weeks postpartum were 23.4% and 40.6% (P<.001), and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6% and 27.8% (P=.76) and 27.7% and 32.8% (P=.21). Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia, but it did not affect perinatal HIV transmission.", "A previous trial in Nepal showed that supplementation with vitamin A or its precursor (betacarotene) in women of reproductive age reduced pregnancy-related mortality by 44% (95% CI 16-63). We assessed the effect of vitamin A supplementation in women in Ghana.\n ObaapaVitA was a cluster-randomised, double-blind, placebo-controlled trial undertaken in seven districts in Brong Ahafo Region in Ghana. The trial area was divided into 1086 small geographical clusters of compounds with fieldwork areas consisting of four contiguous clusters. All women of reproductive age (15-45 years) who gave informed consent and who planned to remain in the area for at least 3 months were recruited. Participants were randomly assigned by cluster of residence to receive a vitamin A supplement (25 000 IU retinol equivalents) or placebo capsule orally once every week. Randomisation was blocked and based on an independent, computer-generated list of numbers, with two clusters in each fieldwork area allocated to vitamin A supplementation and two to placebo. Capsules were distributed during home visits undertaken every 4 weeks, when data were gathered on pregnancies, births, and deaths. Primary outcomes were pregnancy-related mortality and all-cause female mortality. Cause of death was established by verbal post mortems. Analysis was by intention to treat (ITT) with random-effects regression to account for the cluster-randomised design. Adverse events were synonymous with the trial outcomes. This trial is registered with ClinicalTrials.gov, number NCT00211341.\n 544 clusters (104 484 women) were randomly assigned to vitamin A supplementation and 542 clusters (103 297 women) were assigned to placebo. The main reason for participant drop out was migration out of the study area. In the ITT analysis, there were 39 601 pregnancies and 138 pregnancy-related deaths in the vitamin A supplementation group (348 deaths per 100 000 pregnancies) compared with 39 234 pregnancies and 148 pregnancy-related deaths in the placebo group (377 per 100 000 pregnancies); adjusted odds ratio 0.92, 95% CI 0.73-1.17; p=0.51. 1326 women died in 292 560 woman-years in the vitamin A supplementation group (453 deaths per 100 000 years) compared with 1298 deaths in 289 310 woman-years in the placebo group (449 per 100 000 years); adjusted rate ratio 1.01, 0.93-1.09; p=0.85.\n The body of evidence, although limited, does not support inclusion of vitamin A supplementation for women in either safe motherhood or child survival strategies.\n UK Department for International Development, and USAID.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "Young infants are at risk of vitamin A deficiency. Supplementation of breastfeeding mothers improves the vitamin A status of their infants, but there are no data regarding its effect on infant mortality, and data on the effect of directly supplementing infants during the first few weeks of life are conflicting.\n The objective was to measure the effect on infant mortality of supplementing neonates and their HIV-negative mothers with single, large doses of vitamin A during the immediate postpartum period.\n A randomized, placebo-controlled, 2-by-2 factorial design trial was conducted in 14,110 mothers and their infants; 9208 of the mothers were HIV-negative at delivery, remained such during the postpartum year, and were retained in the current analysis. The infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A (Aa), mothers received vitamin A and infants received placebo (Ap), mothers received placebo and infants received vitamin A (Pa), and both mothers and infants received placebo (Pp). The vitamin A dose in the mothers was 400,000 IU and in the infants was 50,000 IU. The mother-infant pairs were followed to 12 mo.\n Hazard ratios (95% CI) for 12 mo mortality among infants in the maternal-supplemented and infant-supplemented groups were 1.17 (0.87, 1.58) and 1.08 (0.80, 1.46), respectively. Hazard ratios (95% CI) for the Aa, Ap, and Pa groups compared with the Pp group were 1.28 (0.83, 1.98), 1.27 (0.82, 1.97), and 1.18 (0.76, 1.83), respectively. These data indicate no overall effect. Serum retinol concentrations among a subsample of women were similar to reference norms.\n Postpartum maternal or neonatal vitamin A supplementation may not reduce infant mortality in infants of HIV-negative women with an apparently adequate vitamin A status.", "Community trials of the efficacy of vitamin A supplementation in reducing preschool childhood mortality have produced conflicting results. To resolve the question, a randomised, double-masked, placebo-controlled community trial of 28,630 children aged 6-72 months was carried out in rural Nepal, an area representative of the Gangetic flood plain of South Asia. Randomisation was carried out by administrative ward; the vitamin-A-supplemented children received 60,000 retinol equivalents every 4 months and placebo-treated children received identical capsules containing 300 retinol equivalents. After 12 months, the relative risk of death in the vitamin-A-supplemented compared with the control group was 0.70 (95% confidence interval 0.56-0.88), equivalent to a 30% reduction in mortality. The trial, which had been planned to last 2 years, was discontinued. The reduction in mortality was present in both sexes (relative risk for boys 0.77; for girls 0.65), at all ages (range of relative risks 0.83-0.50), and throughout the year (0.76-0.67). The reduction in mortality risk was not affected by acute nutritional status, as measured by arm circumference. Thus, periodic vitamin A delivery in the community can greatly reduce child mortality in developing countries.", "We assessed the effect of supplementing newborns with 50000 IU of vitamin A on all-cause infant mortality through 24 weeks of age.\n This was a community-based, double-masked, cluster-randomized, placebo-controlled trial conducted in 19 unions in rural northwest Bangladesh. The study was nested into and balanced across treatment arms of an ongoing placebo-controlled, weekly maternal vitamin A or beta-carotene supplementation trial. Study-defined sectors (N = 596) were evenly randomized for newborns of participating mothers to receive a single, oral supplement of vitamin A (50000 IU) or placebo as droplets of oil squeezed from a gelatinous capsule. Mothers provided informed consent for newborn participation at approximately 28 weeks' gestation. After birth, typically at home (where >90% of births occurred), infants were supplemented and their vital status was followed through 24 weeks of age. The main outcome measure was mortality through 24 weeks of age.\n We obtained maternal consent to dose 17116 live-born infants (99.8% of all eligible) among whom 15937 (93.1%) were visited to be supplemented <30 days after birth and for whom vital status at 24 weeks of age was known. Dosed infants (n = 15902 [99.8%]) received their study supplement at a median age of 7 hours. Relative to control subjects, the risk of death in vitamin A-supplemented infants was 0.85, reflecting a 15% reduction in all-cause mortality. Protective relative risks were indistinguishable by infant gender, gestational age, birth weight, age at dosing, maternal age, parity, or across the 3 treatment arms of the maternal supplementation trial.\n Newborn vitamin A dosing improved infant survival through the first 6 months of life in Bangladesh. These results corroborate previous findings from studies in Indonesia and India and provide additional evidence that vitamin A supplementation shortly after birth can reduce infant mortality in South Asia.", "Although most studies on the effect of vitamin A supplementation have reported reductions in childhood mortality, the effects on morbidity are less clear. We have carried out two double-blind, randomised, placebo-controlled trials of vitamin A supplementation in adjacent populations in northern Ghana to assess the impact on childhood morbidity and mortality. The Survival Study included 21,906 children aged 6-90 months in 185 geographical clusters, who were followed for up to 26 months. The Health Study included 1455 children aged 6-59 months, who were monitored weekly for a year. Children were randomly assigned either 200,000 IU retinol equivalent (100,000 IU under 12 months) or placebo every 4 months; randomisation was by individual in the Health Study and by cluster in the Survival Study. There were no significant differences in the Health Study between the vitamin A and placebo groups in the prevalence of diarrhoea or acute respiratory infections; of the symptoms and conditions specifically asked about, only vomiting and anorexia were significantly less frequent in the supplemented children. Vitamin-A-supplemented children had significantly fewer attendances at clinics (rate ratio 0.88 [95% CI 0.81-0.95], p = 0.001), hospital admissions (0.62 [0.42-0.93], p = 0.02), and deaths (0.81 [0.68-0.98], p = 0.03) than children who received placebo. The extent of the effect on morbidity and mortality did not vary significantly with age or sex. However, the mortality rate due to acute gastroenteritis was lower in vitamin-A-supplemented than in placebo clusters (0.66 [0.47-0.92], p = 0.02); mortality rates for all other causes except acute lower respiratory infections and malaria were also lower in vitamin A clusters, but not significantly so. Improving the vitamin A intake of young children in populations where xerophthalmia exists, even at relatively low prevalence, should be a high priority for health and agricultural services in Africa and elsewhere.", "Nutritional anaemia, thought to be caused by iron deficiency, affects 50-70% of pregnant women in the developing world. The influence of vitamin A and iron supplementation was studied in anaemic pregnant women in West Java, in a randomised, double-masked, placebo-controlled field trial. 251 women aged 17-35 years, parity 0-4, gestation 16-24 weeks, and haemoglobin between 80 and 109 g/L were randomly allocated to four groups: vitamin A (2.4 mg retinol) and placebo iron tablets; iron (60 mg elemental iron) and placebo vitamin A; vitamin A and iron; or both placebos, all daily for 8 weeks. Maximum haemoglobin was achieved with both vitamin A and iron supplementation (12.78 g/L, 95% Cl 10.86 to 14.70), with one-third of the response attributable to vitamin A (3.68 g/L, 2.03 to 5.33) and two-thirds to iron (7.71 g/L, 5.97 to 9.45). After supplementation, the proportion of women who became non-anaemic was 35% in the vitamin-A-supplemented group, 68% in the iron-supplemented group, 97% in the group supplemented with both, and 16% in the placebo group. Improvement in vitamin A status may contribute to the control of anaemic pregnant women.", "The effect of vitamin A supplementation on the survival of infants aged <6 mo is unclear. Because most infant deaths occur in the first few month of life, maternal supplementation may improve infant survival.\n The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants <6 mo of age.\n Married women of reproductive age in 270 wards of Sarlahi district, Nepal, were eligible to participate. Wards were randomly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate (vitamin A), 42 mg all-trans-beta-carotene, or placebo. Pregnancies were followed until miscarriage, stillbirth, maternal death, or live birth of one or more infants, who were followed through 24 wk of age.\n A total of 43559 women were enrolled; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial. The rate of fetal loss was 92.0/1000 pregnancies in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.06 (95% CI: 0.91, 1.25) and 1.03 (95% CI: 0.87, 1.19), respectively. The 24-wk mortality rate was 70.8/1000 live births in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.05 (95% CI: 0.87, 1.25) and 1.03 (95% CI: 0.86, 1.22), respectively.\n Small weekly doses of vitamin A or beta-carotene given to women before conception, during pregnancy, and through 24 wk postpartum did not improve fetal or early infant survival in Nepal." ]

[ "19572992", "10464834", "10227321", "1391559", "11786454", "15297305", "10934078", "10337455", "1889273" ]

[ "Management of bronchiolitis without antibiotics: a multicentre randomized control trial in Bangladesh.", "Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa.", "Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults.", "[Antibiotic treatment for acute episodes of chronic obstructive pulmonary disease].", "Reducing antibiotic use for acute bronchitis in primary care: blinded, randomised controlled trial of patient information leaflet.", "Effectiveness of a multiple intervention to reduce antibiotic prescribing for respiratory tract symptoms in primary care: randomised controlled trial.", "Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription.", "Efficacy and tolerability of myrtol standardized in long-term treatment of chronic bronchitis. A double-blind, placebo-controlled study. Study Group Investigators.", "Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen." ]

[ "To ascertain that antibiotics have no role in the management of bronchiolitis.\n Multicentre randomized control trial (RCT).\n Five purposively selected teaching hospitals in Bangladesh.\n Children under 24 months old with bronchiolitis.\n Children were randomized into three groups of therapeutic interventions: parenteral ampicillin (P-Ab), oral erythromycin (O-Ab) and no antibiotic (N-Ab) in adjunct to supportive measures.\n Clinical improvement was assessed using 18 symptoms/signs which were graded on a two-point recovery scale of 'rapid' and 'gradual', indicating improvement within 'four days' and 'beyond four days', respectively.\n Each intervention group consisted of 98 +/- 1 children having comparable clinico-epidemiological characteristics at the baseline. The trial revealed that most chesty features (features appearing to arise from chest, i.e. cough, breathing difficulty, wheeze, chest indrawing, tachypnoea, tachycardia, rhonchi and crepitation) demonstrated a gradual recovery, beyond 4th admission day and, not differing among the three intervention groups (p > 0.23, p < 0.62, p = 0.54, p < 0.27, p = 0.75, p = 0.76, p = 0.81, p > 0.98, respectively). Most non-chesty features (features appearing to arise away from chest, i.e. feeding/sleeping difficulties, social smile, restlessness, inconsolable crying, nasal flaring, fever and hypoxaemia) demonstrated a rapid recovery, within 4 days, remaining comparable among the three intervention groups (p < 0.07, p = 0.65, p = 0.24, p < 0.61, p = 0.22, p = 0.84, p = 0.29 and p = 0.96, respectively). However, nasal symptoms (runny nose and nasal blockage) also showed no difference among groups (p = 0.36 and p = 0.66, respectively). Thus, the dynamics of clinical outcome obviates that children not receiving antibiotics had similar clinical outcome than those who did.\n In hospital settings, managing bronchiolitis with only supportive measures but without antibiotics remains preferable.", "The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.", "The emergence and spread of antibiotic-resistant Streptococcus pneumoniae in US communities is due, in part, to the excessive use of antibiotics for acute respiratory tract infections.\n To decrease total antibiotic use for uncomplicated acute bronchitis in adults.\n Prospective, nonrandomized controlled trial, including baseline (November 1996-February 1997) and study (November 1997-February 1998) periods.\n Four selected primary care practices belonging to a group-model health maintenance organization in the Denver, Colo, metropolitan area.\n Consecutive adults diagnosed as having uncomplicated acute bronchitis. A total of 2462 adults were included at baseline and 2027 adults were included in the study. Clinicians included 56 physicians, 28 physician assistants or nurse practitioners, and 9 registered nurses.\n The full intervention site received household and office-based patient educational materials, as well as a clinician intervention consisting of education, practice-profiling, and academic detailing. A limited intervention site received only office-based educational materials, and control sites provided usual care.\n Antibiotic prescriptions for uncomplicated acute bronchitis during baseline and study periods.\n Antibiotic prescription rates for uncomplicated acute bronchitis were similar at all 4 sites during the baseline period. During the study period, there was a substantial decline in antibiotic prescription rates at the full intervention site (from 74% to 48% [P = .003]), but not at the control and limited intervention sites (78% to 76% [P = .81] and 82% to 77% [P = .68], respectively). Compared with control sites, changes in nonantibiotic prescriptions (inhaled bronchodilators, cough suppressants, and analgesics) were not significantly different for intervention sites. Return office visits (within 30 days of the incident visit) for bronchitis or pneumonia did not change significantly for any of the sites.\n Antibiotic treatment of adults diagnosed as having uncomplicated acute bronchitis can be safely reduced using a combination of patient and clinician interventions.", "Antibiotic therapy for acute episodes of chronic obstructive pulmonary disease (COPD) is a controversial issue still not clarified. In order to evaluate the effectivity of the antibiotic therapy, we designed a double-blind controlled and randomized clinical trial, in which 90 patients hospitalized due to an acute episode of COPD were divided into three groups: group I, cotrimoxazole (29 patients); group II, amoxicillin-clavulanic acid (32 patients) and group III, placebo (29 patients). Gasometric and spirometric measures were taken in addition to clinical evaluation at hospital admission and discharge using a numerical valoration system. All patients were treated with common bronchodilators. The three groups were homogeneous at their admission and there were no statistical differences at their discharge. We conclude that antibiotics do not play a relevant role in the improvement of acute episodes of COPD.", "To assess whether sharing the uncertainty of the value of antibiotics for acute bronchitis in the form of written and verbal advice affects the likelihood of patients taking antibiotics.\n Nested, single blind, randomised controlled trial.\n Three suburban general practices in Nottingham Participants: 259 previously well adults presenting with acute bronchitis.\n In group A, 212 patients were judged by their general practitioner not to need antibiotics that day but were given a prescription to use if they got worse and standard verbal reassurance. Half of them (106) were also given an information leaflet. All patients in group B (47) were judged to need antibiotics and were given a prescription and encouraged to use it.\n Antibiotic use in the next two weeks. Reconsultation for the same symptoms in the next month.\n In group A fewer patients who received the information leaflet took antibiotics compared with those who did not receive the leaflet (49 v 63, risk ratio 0.76, 95% confidence interval 0.59 to 0.97, P=0.04). Numbers reconsulting were similar (11 v 14). In group B, 44 patients took the antibiotics.\n Most previously well adults with acute bronchitis were judged not to need antibiotics. Reassuring these patients and sharing the uncertainty about prescribing in a information leaflet supported by verbal advice is a safe strategy and reduces antibiotic use.", "To assess the effectiveness of a multiple intervention aimed at reducing antibiotic prescription rates for symptoms of the respiratory tract in primary care.\n Randomised controlled trial.\n Twelve peer review groups including 100 general practitioners with their collaborating pharmacists in the region of Utrecht, Netherlands.\n The intervention consisted of group education meetings, with a consensus procedure on indication for and type of antibiotics and with training in communication skills; monitoring and feedback on prescribing behaviour; group education for assistants of general practitioners and pharmacists; and education material for patients. The control group did not receive any of these elements.\n Antibiotic prescription rates for acute symptoms of the respiratory tract and patients' satisfaction.\n 89 general practitioners completed the study (89%). At baseline, prescription rates for antibiotics for respiratory tract symptoms did not differ between intervention and control group (27% v 29%, respectively). After nine months, the prescription rates in the intervention group fell to 23%, whereas the control group's rose to 37% (mean difference in change -12%, 95% confidence interval -18.9% to -4.0%). Multilevel analysis confirmed the results of the unadjusted analysis (intervention effect -10.7%, -20.3% to -1.0%). Patients' satisfaction was high and did not differ in the two groups at baseline or after the intervention.\n A multiple intervention reduced prescribing rates of antibiotics for respiratory tract symptoms while maintaining a high degree of satisfaction among patients. Further research should focus on the sustainability and cost effectiveness of this intervention.", "Inappropriate antibiotic use for pulmonary infiltrates is common in the intensive care unit (ICU). We sought to devise an approach that would minimize unnecessary antibiotic use, recognizing that a gold standard for the diagnosis of nosocomial pneumonia does not exist. In a randomized trial, clinical pulmonary infection score (CPIS) (Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D. Lew, and P. M. Suter. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic \"blind\" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129) was used as operational criteria for decision-making regarding antibiotic therapy. Patients with CPIS </= 6 (implying low likelihood of pneumonia) were randomized to receive either standard therapy (choice and duration of antibiotics at the discretion of physicians) or ciprofloxacin monotherapy with reevaluation at 3 d; ciprofloxacin was discontinued if CPIS remained </= 6 at 3 d. Antibiotics were continued beyond 3 d in 90% (38 of 42) of the patients in the standard as therapy compared with 28% (11 of 39) in the experimental therapy group (p = 0.0001). In patients in whom CPIS remained </= 6 at the 3 d evaluation point, antibiotics were still continued in 96% (24 of 25) in the standard therapy group but in 0% (0 of 25) of the patients in the experimental therapy group (p = 0.0001). Mortality and length of ICU stay did not differ despite a shorter duration (p = 0.0001) and lower cost (p = 0.003) of antimicrobial therapy in the experimental as compared with the standard therapy arm. Antimicrobial resistance, or superinfections, or both, developed in 15% (5 of 37) of the patients in the experimental versus 35% (14 of 37) of the patients in the standard therapy group (p = 0.017). Thus, overtreatment with antibiotics is widely prevalent, but unnecessary in most patients with pulmonary infiltrates in the ICU. The operational criteria used, regardless of the precise definition of pneumonia, accurately identified patients with pulmonary infiltrates for whom monotherapy with a short course of antibiotics was appropriate. Such an approach led to significantly lower antimicrobial therapy costs, antimicrobial resistance, and superinfections without adversely affecting the length of stay or mortality.", "This multicenter, placebo-controlled, double-blind, randomized parallel-group trial was conducted to investigate the efficacy and tolerability of myrtol standardized (MYS, Gelomyrtol forte, 3 x 300 mg) in the long-term treatment of patients with chronic bronchitis during the winter. 246 patients received the investigational treatments (MYS: 122, placebo: 124) for at least 1 month; 215 subjects (110 under MYS and 105 under placebo) were evaluable in terms of efficacy (exacerbation rate, the need for antibiotics, symptom scores and general well-being) for the protocol-defined 6 months of treatment. Statistically significantly (p < 0.01) more patients remained without acute exacerbation in the myrtol standardized group (72%) compared to the placebo group (53%). In the placebo group, there was an evident peak in the incidence of exacerbations during the third month of treatment, which was not observed in the active treatment group. In the MYS group, 51.6% of the patients with an acute exacerbation required antibiotics vs. 61.2% under placebo. 62.5% of the patients treated with antibiotics in the MYS group required them for < or = 7 days, whereas 76.7% of the patients in the placebo group treated with antibiotics for exacerbation needed antibiotics for > 7 days. Well-being (assessed in terms of general health and health impairment by cough and expectoration) was significantly better under treatment with MYS. The overall therapeutic efficacy evaluation scored higher for MYS. Therefore, it is concluded that long-term treatment with MYS is equally well tolerated as placebo but is clearly superior in efficacy in terms of protecting against acute exacerbations in patients with chronic bronchitis: it reduces the frequency and intensity of acute exacerbations, the need of antibiotics for them and the health impairment by cough and expectoration.", "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." ]

[ "3511372", "2189149", "16773409", "11752031", "8897562", "109598", "11040176", "12722031", "9048349" ]

[ "Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs.", "The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party.", "Effect of fosinopril in children with steroid-resistant idiopathic nephrotic syndrome.", "Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy.", "Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis. A report of the International Study of Kidney Disease in Children.", "Nephrotic syndrome in children: a randomized trial comparing two prednisone regimens in steroid-responsive patients who relapse early. Report of the international study of kidney disease in children.", "A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease.", "Controlled, prospective trial of steroid treatment in IgA nephropathy: a limitation of low-dose prednisolone therapy.", "Late prednisone withdrawal in cyclosporine-treated kidney transplant patients: a randomized study." ]

[ "We evaluated renal function in 107 patients with active lupus nephritis who participated in long-term randomized therapeutic trials (median follow-up, seven years). For patients taking oral prednisone alone, the probability of renal failure began to increase substantially after five years of observation. Renal function was better preserved in patients who received various cytotoxic-drug therapies, but the difference was statistically significant only for intravenous cyclophosphamide plus low-dose prednisone as compared with high-dose prednisone alone (P = 0.027). The advantage of treatment with intravenous cyclophosphamide over oral prednisone alone was particularly apparent in the high-risk subgroup of patients who had chronic histologic changes on renal biopsy at study entry. Patients treated with intravenous cyclophosphamide have not experienced hemorrhagic cystitis, cancer, or a disproportionate number of major infections. We conclude that, as compared with high-dose oral prednisone alone, treatment of lupus glomerulonephritis with intravenous cyclophosphamide reduces the risk of end-stage renal failure with few serious complications.", "We have assessed the medium-term effect of a short course of high-dose, alternate-day prednisolone on adult nephrotic patients with membranous nephropathy, using a randomized, prospective, double-blind, controlled trial. Patients were entered over the period 1981 to 1984 and were observed for a minimum of three years. One hundred and seven adult patients who had not previously received immunosuppressive treatment were included in the trial. One hundred and sixty further patients, excluded from the trial, but with membranous nephropathy were identified, followed and assessed retrospectively at the end of the trial. At 36 months there was no significant difference between control and treatment groups in plasma creatinine, creatinine clearance or 24-h excretion of protein. At between three and six months serum albumin concentrations were higher and protein excretions lower in the treatment group compared to controls. No significant benefit was therefore observed on renal function in the medium term.", "We aimed to test if fosinopril reduces urinary protein excretion and alleviates renal tubular damage in normotensive children with steroid-resistant idiopathic nephrotic syndrome (SRINS). We also aimed to evaluate whether there are changes in steady-state blood pressure and serum concentrations of serum angiotensin-converting enzyme (ACE) and plasma renin activity or angiotensin II (AT-II) in children under this treatment. Forty-five normotensive patients with SRINS were randomly divided into two groups. Group I was treated with fosinopril and prednisone for 12 weeks, while group II was treated with prednisone alone for the same duration. The values of 24-h urinary protein excretion were 1.25+/-0.64 vs 2.52+/-0.56 g/24 h (P<0.05), 1.16+/-0.45 vs 2.42+/-0.24 g/24 h (P<0.05), and 1.10+/-0.41 vs 2.05+/-0.46 g/24 h (P<0.05) in group I and group II patients, respectively, at 4, 8, and 12 weeks. Patients in group I showed lower serum concentrations of urinary retinol-binding protein and beta(2)-microglobulin (P<0.01) at the end of the study, but the patients' blood pressure and components of the renin-angiotensin system (RAS) had no change during treatment. The result suggested that fosinopril significantly reduced proteinuria and alleviated renal tubular damage, but did not influence blood pressure and components of systemic RAS in normotensive children with SRINS.", "In a single-center, multiple-referral source study, 38 patients with progressive IgA nephropathy and controlled hypertension were randomized to treatment with prednisolone and cytotoxic agents, to therapy with low-dose cyclophosphamide then azathioprine, and to control groups. The follow-up period lasted 2 to 6 yr. Renal survival, as assessed by Kaplan-Meier analysis annually to 5 yr, showed significant preservation of function from 3 yr in the treatment group and 82, 82, 72, and 72% for 2, 3, 4, and 5 yr, respectively, compared with 68, 47, 26, and 6% in controls. Rate of loss of renal function, evaluated objectively by least-squares analyses of reciprocal serum creatinine, was reduced-and in one-third of the patients, arrested-during immunosuppressive treatment. Proteinuria, present in all patients at the time of entry into the trial, was reduced by treatment from 12 mo, compared with pretreatment levels or controls; erythrocyturia was reduced from 6 mo. Histologic activity and chronicity indexes were determined in renal biopsies performed at trial entry. Multivariate analysis demonstrated that mesangial cell proliferation and matrix scores were highest in those patients with more rapidly progressive disease. No morphologic variable or residual renal function predicted response to immunosuppressive therapy at entry. Mean arterial pressures did not differ significantly between treatment and control groups. There was thus no explanation other than treatment for the improved outcome in patients who received immunosuppressive therapy. Morbidity attributable to treatment or to renal failure occurred in both groups; an audit showed that benefits of therapy outweighed expected or minor side effects of drugs in this population at risk of end-stage renal failure. Patients selected for moderately progressive IgA nephropathy benefit from treatment with prednisolone and cytotoxic agents; results are consistent with modulation of systemic immune response or nephritic injury, thus explaining improved outcome, and indicate that this therapy has an acceptably low risk of side effects.", "Sixty children, with biopsy diagnosed focal segmental glomerulosclerosis (FSGS) and with unremitting nephrotic syndrome despite intensive therapy with adrenocortical steroids, were randomly allocated into a clinical trial comparing prednisone, 40 mg/m2 on alternate days for a period of 12 months (control group), with the same prednisone regimen plus a 90-day course of daily cyclophosphamide, 2.5 mg/kg in a single morning dose (experimental group). One-quarter of the children in each group had complete resolution of proteinuria. The proportions of children with increased, unchanged, and decreased proteinuria by the end of the study were the same in the two groups. Treatment failure was defined as an increase in serum creatinine of 30% or more or greater than 0.4 mg/dl, or onset of renal failure. Treatment failure occurred in 36% of the control group and 57% of the experimental group (P > 0.1). Five patients died during the trial, 3 in the experimental group and 2 in the control group. A Kaplan-Meier survival analysis revealed no significant differences between the two groups. Cyclophosphamide therapy for children with steroid-resistant FSGS is not recommended.", "Fifty-four children with steroid-responsive nephrotic syndrome relapsing within 6 months of their initial response were randomly allocated to receive two different regimens of prednisone therapy. The test regimen differed from the standard prednisone relapse regimen used by the International Study of Kidney Disease in Children in that the total dosage was about double, and the duration of daily therapy (8 weeks vs. a mean of 12 days) as well as the total duration of treatment (8 weeks vs. a mean of approximately 6 weeks) was longer. The proportion of patients relapsing during treatment was significantly smaller (8% vs. 40%) and the length of remission following treatment was significantly longer (3.27 vs. 1.48 months) in the test group. All patients in both groups relapsed by 8 months. During a period of approximately 6 months after this relapse, neither the frequency of relapses nor the mean number of days of proteinuria differed significantly. Opinions of participants in this multicenter trial varied concerning whether these statistically significant differences clinically justified exposing patients to the more intensive treatment regimen. However, all agreed that neither form of treatment was satisfactory in terms of preventing subsequent relapses.", "Clinical experience suggests that 6-mercaptopurine (6-MP) is effective therapy for children with active steroid-dependent Crohn's disease (CD). We report the results of a prospective, placebo-controlled, multicenter trial evaluating the combination of 6-MP and prednisone as therapy for children with newly diagnosed moderate-to-severe CD.\n Fifty-five children (age, 13+/-2 years) were randomized to treatment with 6-MP (1.5 mg x kg(-1) x day(-1)) or placebo within 8 weeks of initial diagnosis. Both groups also received prednisone (40 mg/day). Prednisone dosage adjustments were based on a defined schedule determined by the change in a subject's disease activity score, and steroid administration was discontinued as remission was achieved. Study treatment with 6-MP or placebo continued for 18 months.\n Groups were comparable for age, sex, and site and activity of disease. In the 6-MP group, the duration of steroid use was shorter (P<0.001) and the cumulative steroid dose lower at 6, 12, and 18 months (P<0.01). Although remission was induced in 89% of both groups, only 9% of the remitters in the 6-MP group relapsed compared with 47% of controls (P = 0.007). Growth was comparable in both groups. No clinically significant adverse events occurred, although mild leukopenia and increases in aminotransferase activity were noted in the 6-MP group.\n Addition of 6-MP to a regimen of corticosteroids significantly lessens the need for prednisone and improves maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe CD.", "No accepted therapy has been established for progressive immunoglobulin A (IgA) nephropathy.\n A prospective, randomized, controlled trial of low-dose prednisolone therapy was performed in patients with IgA nephropathy with moderate histological characteristics. Forty-three patients in the steroid group and 47 patients in the control group were included in the study. The initial dose of prednisolone was 20 mg/d, gradually tapered to 5 mg/d during 2 years.\n Baseline urine protein-creatinine ratio (UP-UCR) was significantly greater in the steroid group than in controls. Follow-up duration was 65 +/- 25 months in the steroid group and 64 +/- 23 months in controls. Changes in UP-UCR from baseline, ie, UP-UCR at last follow-up minus UP-UCR at baseline, were significantly lower in the steroid group than in controls (steroid group, -0.84 +/- 1.78; controls, 0.26 +/- 1.65; P = 0.0034). Kidney survival was similar in both groups. Patients were divided into two subgroups according to clinical course. There were 28 improved patients and 15 unimproved patients in the steroid group and 27 improved patients and 20 unimproved patients in the control group. In the steroid group, UP-UCR was significantly greater in the unimproved than improved subgroup (3.1 +/- 2.6 versus 1.8 +/- 1.5).\n These data suggest that our protocol had an antiproteinuric effect, but could not improve kidney survival. Because the effect of steroid therapy to prevent the progression of IgA nephropathy is believed to be linked closely to reduction in urinary protein, an insufficient dose of prednisolone in our protocol may be the reason for the discrepancy between the effect on proteinuria and kidney survival.", "Prednisone in combination with cyclosporine and/or azathioprine is commonly used after kidney transplantation to prevent graft rejection. Long-term use of prednisone can give rise to multiple side effects and morbidity. This randomized study was conducted to find out if prednisone could be withdrawn in recipients at least 1 yr after kidney transplantation. Eighty-four such recipients of a cadaveric kidney with stable renal function on cyclosporine and prednisone were randomized to continue prednisone (N = 42) or to withdraw prednisone in a 2-month period (N = 42). The main end point was the percentage of successful prednisone withdrawal. Both groups were compared for the incidence of infections and cardiovascular risk factors and for the incidence and cause of deterioration of renal function. All patients had a 14-month follow-up. In 67% (N = 28) of the patients, prednisone could be withdrawn successfully. Acute rejection was the main cause of withdrawal failure (N = 11, 26%). No grafts were lost due to rejection. In the prednisone withdrawal group, a tendency was noted for a lower incidence of infections (difference: 17%; 95% confidence interval [CI]: -4% to 37%). After withdrawal, less antihypertensive drugs were necessary to control hypertension (difference: 0.5 drugs/patient; 95% CI: -0.9 to -0.1) and 35% less patients (23 of 41 versus nine of 42) needed cholesterol-lowering drugs (95% CI: -54% to -15%). A reduction of the frequency of patients with Type II diabetes mellitus was found (difference 10%; 95% CI: -24% to 5%) with a decrease of glycosylated hemoglobin (difference: 0.4 mmol/L; 95% CI: 0.1 to 0.8). Disappearance of moonface was found in 25% of the patients. Elective withdrawal of prednisone > 1 yr after postmortal kidney transplantation can be accomplished safely provided that patients are controlled frequently. Beneficial effects were found regarding hypertension, hypercholesterolemia, hyperglycemia, and appearance." ]