Datasets:

allenai
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mslr2022

review_id stringlengths 8 8	pmid sequence	title sequence	abstract sequence	target stringlengths 56 2.23k
CD007697	[ "16394043" ]	[ "Aggressive surgical effort and improved survival in advanced-stage ovarian cancer." ]	[ "Residual disease after initial surgery for ovarian cancer is the strongest prognostic factor for survival. However, the extent of surgical resection required to achieve optimal cytoreduction is controversial. Our goal was to estimate the effect of aggressive surgical resection on ovarian cancer patient survival.\n A retrospective cohort study of consecutive patients with International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer undergoing primary surgery was conducted between January 1, 1994, and December 31, 1998. The main outcome measures were residual disease after cytoreduction, frequency of radical surgical resection, and 5-year disease-specific survival.\n The study comprised 194 patients, including 144 with carcinomatosis. The mean patient age and follow-up time were 64.4 and 3.5 years, respectively. After surgery, 131 (67.5%) of the 194 patients had less than 1 cm of residual disease (definition of optimal cytoreduction). Considering all patients, residual disease was the only independent predictor of survival; the need to perform radical procedures to achieve optimal cytoreduction was not associated with a decrease in survival. For the subgroup of patients with carcinomatosis, residual disease and the performance of radical surgical procedures were the only independent predictors. Disease-specific survival was markedly improved for patients with carcinomatosis operated on by surgeons who most frequently used radical procedures compared with those least likely to use radical procedures (44% versus 17%, P < .001).\n Overall, residual disease was the only independent predictor of survival. Minimizing residual disease through aggressive surgical resection was beneficial, especially in patients with carcinomatosis.\n II-2." ]	We found only low quality evidence comparing ultra-radical and standard surgery in women with advanced ovarian cancer and carcinomatosis. The evidence suggested that ultra-radical surgery may result in better survival. It was unclear whether there were any differences in progression-free survival, QoL and morbidity between the two groups. The cost-effectiveness of this intervention has not been investigated. We are, therefore, unable to reach definite conclusions about the relative benefits and adverse effects of the two types of surgery. In order to determine the role of ultra-radical surgery in the management of advanced stage ovarian cancer, a sufficiently powered randomised controlled trial comparing ultra-radical and standard surgery or well-designed non-randomised studies would be required.
CD000174	[ "8627434", "2677294", "3373404", "3321891", "8201485", "11430325", "3373405", "3174314", "9078828", "3312552", "3906073", "1305392", "3998921", "10730525" ]	[ "Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room.", "Indomethacin reduces the risks of severe intraventricular hemorrhage.", "Administration of indomethacin for the prevention of periventricular-intraventricular hemorrhage in high-risk neonates.", "Early intravenous indomethacin prolongs respiratory support in very low birth weight infants.", "Low-dose indomethacin therapy and extension of intraventricular hemorrhage: a multicenter randomized trial.", "Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.", "Randomized low-dose indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight neonates.", "Prophylactic indomethacin for prevention of intraventricular hemorrhage in premature infants.", "Effects of early indomethacin administration on oxygenation and surfactant requirement in low birth weight infants.", "Prevention of symptomatic patent ductus arteriosus with a single dose of indomethacin.", "Randomized indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight infants.", "[Indomethacin in the prevention of subependymal-intraventricular hemorrhage in preterm newborns with conventional mechanical ventilation].", "Indomethacin therapy on the first day of life in infants with very low birth weight.", "Indomethacin prophylaxis for patent ductus arteriosus (PDA) in infants with a birth weight of less than 1250 grams." ]	[ "To determine whether a course of low-dose indomethacin therapy, when initiated within 24 hours of birth, would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room.\n Ninety infants, with birth weights of 600 to 1250 gm, were entered into a prospective, randomized, controlled trial to receive either indomethacin, 0.1 mg/kg per dose, or placebo less than 24 hours and again every 24 hours for six doses. Echocardiography was performed on day 1 before treatment and on day 7, 24 hours after treatment. A hemodynamically significant patent ductus arteriosus (PDA) was confirmed with an out-of-study echocardiogram, and the nonresponders were treated with standard indomethacin or ligation.\n Forty-three infants received indomethacin (birth weight, 915 +/- 209 gm; gestational age, 26.4 +/- 1.6 weeks; 25 boys), and 47 received placebo (birth weight, 879 +/- 202 gm; gestational age, 26.4 +/- 1.8 weeks; 22 boys) (P = not significant). Of 90 infants, 77 (86%) had a PDA by echocardiogram on the first day of life before study treatment; 84% of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93% in the placebo group. Nine of forty indomethacin-treated infants (21%) were study-dose nonresponders compared with 22 (47%) of 47 placebo-treated infants (p < 0.018). There were no significant differences between both groups in any of the long-term outcome variables, including intraventricular hemorrhage, duration of oxygen therapy, endotracheal intubation, duration of stay in neonatal intensive care unit, time to regain birth weight or reach full caloric intake, incidence of bronchopulmonary dysplasia, and survival. No significant differences were noted in the incidence of oliguria, elevated plasma creatinine concentration, thrombocytopenia, pulmonary hemorrhage, or necrotizing enterocolitis.\n The prophylactic use of low doses of indomethacin, when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room, decreases the incidence of left-to-right shunting at the level of the ductus arteriosus.", "A prospective, random selection, double-blind clinical trial was carried out to determine the efficacy of indomethacin in preventing periventricular-intraventricular hemorrhage (PV-IVH). Babies who were born in our institution, had birth weights less than or equal to 1500 gm, and had no PV-IVH or grade 1 PV-IVH were given either placebo (n = 70) or indomethacin (n = 71), 0.2 mg/kg intravenously at 6 hours of age and 0.1 mg/kg at 18 and 30 hours. Two major outcomes were determined: the development of grades 2 to 4 PV-IVH and the development of severe PV-IVH (i.e., hemorrhages with blood filling greater than 50% of the ventricles and in some cases with associated parenchymal echodensities). Grades 2 to 4 PV-IVH occurred in 16 (23%) of the indomethacin group and 27 (39%) of the placebo group (p less than 0.03). The incidence of severe PV-IVH was 3% in the indomethacin-treated babies and 14% in the control group (p less than 0.02). The influence of other perinatal factors on the incidence of grades 2 to 4 or severe PV-IVH was determined by stepwise logistic regression. Placebo use, early grade 1 PV-IVH, lower birth weight, and higher fraction of inspired oxygen at 6 hours of life were associated with higher estimated odds of the development of grades 2 to 4 PV-IVH. Placebo use, male gender, lower 5-minute Apgar score, and a large base deficit were predictive of severe PV-IVH. Estimated odds ratios of severe PV-IVH with placebo use and male gender were 11.25:1 and 9:1, respectively. Thus indomethacin prophylaxis reduced the relative risk of grades 2 to 4 PV-IVH and severe PV-IVH, but other perinatal variables contributed significantly to the overall risk of PV-IVH.", "One hundred twenty-two preterm infants were enrolled in a placebo-controlled, double-blind trial using intravenous indomethacin for the prevention of periventricular-intraventricular hemorrhage (PVH-IVH). Before random assignment, data on the infants were stratified according to low-weight (500 to 999 g) or high-weight (1000 to 1500 g) subgroups. Cranial sonography was used to document the absence of PVH-IVH before enrollment and the occurrence of PVH-IVH during the 7-day protocol. Indomethacin, 0.1 mg/kg, or placebo was administered before 12 hours of age and at 24, 48, and 72 hours of age. Five patients receiving indomethacin and six receiving placebo were withdrawn before completion of the study. In the remaining 111 patients, the indomethacin and placebo groups were comparable with respect to gestational ages, maternal complications, Apgar scores, ventilatory requirements, complications of prematurity, and mortality rate. PVH-IVH developed in six of 56 infants who received indomethacin and 11 of 55 infants who received placebo (P = 0.174). Analysis of the individual strata showed that the indomethacin-treated infants in the low-weight subgroup sustained a higher mortality rate (11/17 vs 3/16; P = 0.008) without a reduction in the incidence of PVH-IVH. Infants in the indomethacin-treated high-weight subgroup demonstrated a significantly lower incidence of PVH-IVH (2/39 vs 8/39; P = 0.04), but the frequency of high-grade hemorrhages was comparable for both indomethacin- and placebo-treated groups. In summary, the prophylactic administration of intravenous indomethacin for the prevention of PVH-IVH cannot be recommended for infants less than 1000 g. In preterm infants between 1000 and 1500 g birth weight, indomethacin significantly reduced the incidence of PVH-IVH.", "Infants weighing 1500 g at birth requiring either intermittent positive pressure ventilation or continuous positive airway pressure by 12 hours of age were entered in a randomized double blind controlled trial to test the efficacy of early intravenous indomethacin therapy in preventing chronic pulmonary disease of prematurity. Of the 30 newborns enrolled, 15 were treated with indomethacin and 15 were treated with placebo at 12, 24 and 36 hours of age. The groups were similar for birth weight, gestational age, sex, hyaline membrane disease and intracranial hemorrhage. Infants in the placebo group were successfully weaned from intermittent positive pressure ventilation at an earlier age than infants in the indomethacin group (p less than 0.05). Furthermore, chronic pulmonary disease of prematurity was similar in the two groups despite a reduction in the incidence of patent ductus arteriosus in the indomethacin group.", "We enrolled 61 neonates of 600 to 1250 gm birth weight with evidence of low-grade intraventricular hemorrhage at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that indomethacin (0.1 mg/kg given intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would prevent extension of intraventricular hemorrhage. Twenty-seven infants were assigned to receive indomethacin; 34 infants received saline placebo. There were no significant differences between the two groups in birth weight, gestational age, sex, Apgar scores, percentage of infants treated with surfactant, or distribution of hemorrhages at the time of the first cranial sonogram (echo-encephalogram). Within the first 5 days, 9 of 27 indomethacin-treated and 12 of 34 saline solution-treated infants had extension of their initial intraventricular hemorrhage (p = 1.00). Four indomethacin-treated and three saline solution-treated infants had parenchymal extension of the hemorrhage. Indomethacin was associated with closure of a patent ductus arteriosus by the fifth day of life (p = 0.003). There were no differences in adverse events attributed to indomethacin. We conclude that in very low birth weight infants with low grade intraventricular hemorrhage within the first 6 postnatal hours, prophylactic indomethacin therapy promotes closure of the patent ductus arteriosus and is not associated with adverse events, but does not affect the cascade of events leading to parenchymal involvement of intracranial hemorrhage.", "The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known.\n Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy.\n Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin, 271 (47 percent) died or survived with impairments, as compared with 261 of the 569 infants (46 percent) assigned to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent vs. 50 percent in the placebo group; odds ratio, 0.3; P<0.001) and of severe periventricular and intraventricular hemorrhage (9 percent vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcomes were altered by the prophylactic administration of indomethacin.\n In extremely-low-birth-weight infants, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage.", "We admitted 36 preterm neonates (600 to 1250 gm birth weight) with normal 6-hour echoencephalograms to a randomized, placebo-controlled prospective trial to determine whether a low dose of indomethacin would prevent germinal matrix or intraventricular hemorrhage and permit adequate urinary output. Between the sixth and tenth postnatal hours, indomethacin (0.1 mg/kg) or placebo was administered intravenously every 24 hours for a total of three doses. Cardiac ultrasound studies to assess the status of the ductus arteriosus were performed at 6 postnatal hours and on day 5. Urinary output, serum electrolytes, serum indomethacin levels, and renal and clotting functions were monitored. No differences in birth weight, gestational age, or Apgar scores were noted between the two groups of infants. Two indomethacin-treated infants and three infants given placebo had significant urinary output difficulties, requiring that the study medication be withheld. Of 19 infants given indomethacin, two had germinal matrix or intraventricular hemorrhage, in comparison with 8 of 17 infants given saline solution (p = 0.02). Of the infants who had a left-to-right patent ductus arteriosus shunt before treatment, 64% of the indomethacin-treated and 33% of the saline solution-treated infants no longer had a patent ductus arteriosus on day 5. Ductal status appeared unrelated to the development of germinal matrix or intraventricular hemorrhage.", "The impact of early prophylactic use of intravenous indomethacin on the incidence and severity of periventricular-intraventricular hemorrhage and patent ductus arteriosus in 199 oxygen-requiring premature infants (less than or equal to 1300 g birth weight) was prospectively investigated. The trial was controlled, the infants were randomized, and the investigators were unaware of the group assignments. Patients with minimal (grade I) or no periventricular-intraventricular hemorrhage determined by prestudy echoencephalography were randomized within two birth weight subgroups (500 to 899 and 900 to 1300 g) to receive either prophylactic indomethacin (n = 99) or an equal volume of saline-vehicle placebo (n = 100). The first dose (0.2 mg/kg) was given within 12 hours of delivery and two subsequent doses (0.1 mg/kg) were administered at 12 hourly intervals. Prophylactic indomethacin significantly reduced the incidence of grades II to IV periventricular-intraventricular hemorrhage. Intraventricular hemorrhage was half as common in infants given prophylactic indomethacin as in control infants (23% v 46%, P less than .002). The reduction was manifested in both birth weight subgroups. Results of this study also confirmed a lower incidence of clinically significant patent ductus arteriosus in infants who received prophylactic indomethacin in contrast to those who received placebo (11% v 42%, P less than .001). No significant differences were found between treatment and control groups in the duration of oxygen therapy, mechanical ventilation, or hospitalization or in the incidence of pneumothorax, chronic lung disease, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death. Early prophylactic indomethacin initiated within 12 hours of delivery is effective in reducing the incidence of intraventricular hemorrhage as well as clinically significant patent ductus arteriosus in very low birth weight premature infants.", "A previous study found that early intravenous indomethacin administration prolonged respiratory support in very low birth weight infants. We have, therefore, designed a randomized, double blind controlled study to evaluate the oxygenation, and surfactant requirements in preterm low birth weight infants receiving early indomethacin administration. Premature neonates who received surfactant therapy and on mechanical ventilation were prospectively randomized to receive either placebo or indomethacin (0.2 mg/kg intravenously at 12 postnatal hours and every 24 h for two more doses). Oxygenation was assessed by FiO2 required and arterial/alveolar oxygen (a/A O2) ratio during the first 48 h of life. The doses of surfactant were compared between the two groups. Twenty-seven infants (n = 14 of early indomethacin and n = 13 of placebo group) fulfilled inclusion criteria. At admission to the study, there were no differences in the birth weight, gestational age, sex, Apgar scores, a/A O2 ratio, and FiO2. The control group exhibited a significant improvement in oxygenation (FiO2 requirement and a/A O2 compared with the early indomethacin group at 24 (P = 0.026 and 0.02, respectively) and 48 h of life (P = 0.037 and 0.026, respectively). The requirement of surfactant was significantly larger in the early indomethacin group (P = 0.029). Early indomethacin administration increases oxygen and surfactant requirement.", "To determine the efficacy of indomethacin to prevent the occurrence of symptomatic patent ductus arteriosus (PDA), a randomized clinical trial was conducted involving 32 preterm infants weighing 750 to 1500 g at birth who had hyaline membrane disease. By random assignment, 15 infants were given a single dose of indomethacin, 0.2 mg/kg intravenously, 24 hours after birth. Seventeen infants composed a control group for which indomethacin was reserved as treatment for symptomatic PDA. Birth weight, gestational age, male/female ratio, black/white ratio, and severity of disease were similar for both groups. Only one of the 14 survivors who received prophylactic indomethacin had symptomatic PDA, compared with nine of the 16 survivors in the control group (P = 0.007). There was no difference between the groups in development of bronchopulmonary dysplasia, duration of time endotracheal intubation, was required, duration in oxygen, duration to reach full feedings and regain birth weight, and duration of hospital stay. There was no difference between the two groups in incidence of intraventricular hemorrhage, and none developed necrotizing enterocolitis. These results indicate that the use of prophylactic indomethacin is beneficial in prevention of symptomatic PDA; the lack of differences in pulmonary sequelae or other complications may have been related to a population sample size not large enough to impart sufficient statistical power.", "We admitted 48 preterm neonates (600 to 1250 gm birth weight, normal 6-hour echoencephalograms) to a randomized prospective indomethacin or placebo trial for the prevention of neonatal intraventricular hemorrhage. Beginning at 6 postnatal hours, indomethacin or placebo was administered intravenously every 12 hours for a total of five doses. Cardiac ultrasound studies to assess the status of the ductus arteriosus were performed at 6 postnatal hours and on day 5. Urinary output, serum electrolytes, and renal and clotting functions were monitored. No differences in birth weight, gestational age, Apgar scores, or ventilatory needs were noted between the two groups. Six infants given indomethacin had intraventricular hemorrhage, compared to 14 control infants (P = 0.02). The indomethacin-treated group had significant decreases in serum prostaglandin values 30 hours after the initiation of therapy. The overall incidence of patent ductus arteriosus was 82% at 6 postnatal hours; 84% of the indomethacin-treated infants experienced closure of the ductus, compared to 60% of the placebo-treated patients. Closure of the ductus was not related to incidence of intraventricular hemorrhage. We speculate that indomethacin may provide some protection against neonatal intraventricular hemorrhage by acting on the cerebral microvasculature.", "The results of a double blind study to evaluate the efficiency of prophylactic endovenous indomethacin versus placebo for prevention of intraventricular hemorrhage (IVH) in newborn infants between 28 to 36 weeks of age who were intubated at the delivery room and required mechanical ventilation in NICU are presented. Fourty six patients required mechanical ventilation, but 14 neonates had IVH evaluated by ultrasound when were admitted to the Unit. At least 32 infants were studied, 16 for each group. There were no differences between the groups in weight, gestational age, sex and delivery way. The mobility was the same in relation to hialine membrane disease, sepsis, pneumonie and pneumotorax. The placebo group had more frequency of PDA and mortality (P < 0.5). There were no differences in mean airway pressure and arterial gases, also in glucose, platelets and urinary volume. The indomethacin group had mayor urinary density and FeNa but the results were always in normal ranges. The IVH was the same in both groups. We concluded that the indomethacin at the levels used did not produced alterations, and if the IVH is not prevented, were observed lesser severity of the same and the frequency of PDA and mortality are lesser. But still is necessary more number of cases for best conclusions.", "To investigate the optimal timing for treatment of small premature infants, we performed a double-blind, controlled trial of indomethacin therapy on the first day of life in 104 infants weighing between 700 and 1300 gm. Infants were given indomethacin or placebo at a mean age of 15 hours. Eleven of the 56 infants given placebo developed large left-to-right shunts through a patent ductus arteriosus. In contrast, only two of the 51 infants given indomethacin developed large shunts (P less than 0.025). There were no significant differences in incidence of surgical ligation, duration of oxygen therapy, duration of endotracheal intubation, days required to regain birth weight, or incidence of complications. However, the power of the tests of significance was low because of the small number of patients. Thus, although the incidence of large left-to-right ductus shunts was decreased in the indomethacin group, morbidity was not otherwise altered for the entire group of patients, possibly because of the relatively low incidence (21%) of large shunts in the placebo group. We conclude that although treatment with indomethacin on the first day of life appears to be safe, there is little advantage to its use in centers where the incidence of large shunts through a patent ductus arteriosus is relatively low.", "Very low birth weight (VLBW, less than 1500 g) and extremely low birth weight infants (ELBW, less than 1000 g) are the premature infants that are most likely to develop symptomatic PDA. Intravenous indomethacin has proven effective in prevention of PDA in many prospective trials. This strategy will be a useful adjunctive therapy for premature infants in Thailand.\n To answer the following questions: 1. Will multiple doses of intravenous indomethacin, given to VLBW infants within the first day of life, effectively prevent the occurrence of symptomatic PDA? Are there any side effects or complications? 2. Will this strategy be more beneficial in ELBW?\n The study included thirty VLBW infants born at Ramathibodi Hospital, with birth weights ranging from 630 to 1230 g. They were randomized into 2 groups of 15 infants each. One group received 3 doses of intravenous indomethacin at the dosage of 0.2 mg/kg initially and then 0.1 mg/kg every 12 hours for 2 more doses; the second group received a placebo. The study was performed by a double blind control.\n Sixteen infants developed symptomatic PDA, 4 in the indomethacin group and 12 in the placebo group. The decrease in incidence of PDA is statistically significant. But when the data was analyzed separately for the VLBW and ELBW groups. The effects were only significantly different in ELBW but not yet significant in the VLBW group. There was a statistically significant difference in the incidence of severe intraventricular hemorrhage (IVH) (grade 3 or higher) in the ELBW infants.\n Intravenous indomethacin therapy given to VLBW infants with a birth weight of less than 1250 g decreased incidence of symptomatic PDA with no significant permanent side effects. The effect was markedly noticeable in ELBW infants. Incidence of severe IVH was also markedly decreased in the ELBW infants who received indomethacin." ]	Prophylactic indomethacin has short-term benefits for preterm infants including a reduction in the incidence of symptomatic PDA, PDA surgical ligation, and severe intraventricular haemorrhage. However, there is no evidence of effect on mortality or neurodevelopment.
CD008805	[ "6024144", "4915981" ]	[ "White phosphorus burns and massive hemolysis.", "The treatment of chemical burns: specialized diagnostic, therapeutic, and prognostic considerations." ]	[ "nan", "nan" ]	First aid for phosphorus burns involves the common sense measures of acting promptly to remove the patient's clothes, irrigating the wound(s) with water or saline continuously, and removing phosphorus particles. There is no evidence that using copper sulphate to assist visualisation of phosphorus particles for removal is associated with better outcome, and some evidence that systemic absorption of copper sulphate may be harmful. We have so far been unable to identify any other comparisons relevant to informing other aspects of the care of patients with phosphorus burns. Future versions of this review will take account of information in articles published in languages other than English, which may contain additional evidence based on treatment comparisons.
CD000248	[ "1159434", "14168625", "13969171", "14250709" ]	[ "Trial of long-term anticoagulant therapy in the treatment of small stroke associated with a normal carotid arteriogram.", "CEREBRAL VASCULAR DISEASE IN RELATION TO LONG-TERM ANTICOAGULANT THERAPY.", "Anticoagulant therapy in cerebral infarction. Report on cooperative study.", "CEREBRAL APOPLEXY. A CLINICAL, RADIOLOGICAL, ELECTROENCEPHALOGRAPHIC AND PATHOLOGICAL STUDY WITH SPECIAL REFERENCE TO THE PROGNOSIS OF CEREBRAL INFARCTION AND THE RESULT OF LONG-TERM ANTICOAGULATION THERAPY." ]	[ "The clinical features of 49 patients who had sustained small strokes in the internal carotid artery territory, who were normotensive, free from cardiac or other relevant disease, and who each had a normal appropriate single vessel angiogram are presented. These were randomized into two groups: group A, 25 patients, who received only supportive treatment; group B, 24 patients who were treated with anticoagulants for an average period of 18 months. There was a reduced incidence of neurological episodes during the administration of anticoagulant therapy but, after treatment was discontinued, there was no significant difference between the two groups. In view of the relatively benign prognosis for this syndrome, unless special facilities exist for the personal control of anticoagulant treatment, the dangers may outweigh the benefits.", "nan", "nan", "nan" ]	Compared with control, there was no evidence of benefit from long-term anticoagulant therapy in people with presumed non-cardioembolic ischaemic stroke or transient ischaemic attack, but there was a significant bleeding risk.
CD004431	[ "15240203", "11212135", "6487909", "3693660", "12690582", "11784832", "12883103", "4074113", "10780138", "11777121", "11527284", "8116338", "12583502" ]	[ "Computer-aided retraining of memory and attention in people with multiple sclerosis: a randomized, double-blind controlled trial.", "Neuropsychological counseling improves social behavior in cognitively-impaired multiple sclerosis patients.", "An evaluation of cognitive-behaviour therapy for depression in patients with multiple sclerosis.", "Efficacy of stress-inoculation training in coping with multiple sclerosis.", "A randomized clinical trial of a wellness intervention for women with multiple sclerosis.", "Evaluation of cognitive assessment and cognitive intervention for people with multiple sclerosis.", "Effects of treatment for depression on fatigue in multiple sclerosis.", "Group psychotherapy: benefits in multiple sclerosis.", "Telephone-administered cognitive-behavioral therapy for the treatment of depressive symptoms in multiple sclerosis.", "Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis.", "Unit management of depression of patients with multiple sclerosis using cognitive remediation strategies: a preliminary study.", "Effects of neuropsychological treatment in patients with multiple sclerosis.", "Symptom management and adjustment of patients with multiple sclerosis: a 4-year longitudinal intervention study." ]	[ "Cognitive compromise is one of the main contributing factors to activity and participation restrictions in people with multiple sclerosis (MS). Computer-aided programs are used for retraining memory and attention, but data on the efficacy of these interventions are scarce.\n To assess the efficacy of computer-aided retraining of memory and attention in people with MS impaired in these abilities.\n Randomized, double-blind, controlled trial.\n Outpatients (n=82) with subjective complaints of poor attention or memory, confirmed by a score <80th percentile in at least two tests of the Brief Repeatable Battery of Neuropsychological Tests (BRBNT).\n Participants were randomized to two computer-assisted retraining interventions: memory and attention (study arm), and visuo-constructional and visuo-motor coordination (control arm). Both groups received 16 training sessions over 8 weeks.\n Improvement of 20% or more in at least two BRBNT test scores at 8 weeks compared to baseline (primary end point). Changes in depression and health-related quality of life.\n An improvement occurred in 45% of study patients vs. 43% of control patients (odds ratio 1.07, 95% confidence interval 0.44-2.64). The study treatment was better than the control treatment only on the word list generation test (p=0.016).\n This trial does not support the efficacy of specific memory and attention retraining in MS.", "We studied the effectiveness of a newly-developed cognitive-behavioral intervention in 15 patients with marked cognitive impairment and behavior disorder. The design was a single-blind test of a neuropsychological intervention, with pre- and post-treatment assessments of personality and social behavior. MS patients underwent neurological examination and neuropsychological testing at baseline. The patients were then randomly assigned to neuropsychological counseling or standard, non-specific supportive psychotherapy. The active 12-week treatment emphasized enhancement of insight through education, social skills training, and behavior modification. All patients were re-examined within 2 weeks of the termination of treatment. Neuropsychological technicians were blind to treatment condition. Both groups showed evidence of cognitive impairment and personality/behavior disorder prior to treatment and were well matched on demographic, disability, and cognitive measures. Patients who underwent neuropsychological counseling showed significant positive response on measures of social behavior (e.g. excessive ego-centric speech) compared to those who underwent standard counseling. We conclude that these data support the use of non-pharmacological, neuropsychological counseling in patients with acquired, MS-associated behavior disorder.", "Twenty depressed multiple sclerotic patients were randomly allocated either to cognitive-behaviour therapy or to a waiting list control condition. Assessment of depressive symptoms was conducted at pre-treatment, post-treatment, and a four-week follow-up. In comparison to the waiting list condition, cognitive-behaviour therapy was found to result in clinically and statistically significant improvement on most measures. Although the mechanism by which such treatment achieves its effects is unclear, these results clearly support the use of cognitive-behavioural treatments for depression in this population.", "nan", "To examine the effects of a wellness intervention program for women with multiple sclerosis (MS) on health behaviors and quality of life (QOL).\n Randomized clinical trial.\n Community setting in the southwestern United States.\n Convenience sample of 113 women with physician-confirmed MS (mean age, 45.79y).\n The 2-phase intervention program included lifestyle-change classes for 8 weeks, then telephone follow-up for 3 months. Participants were followed over an 8-month period.\n A series of self-report instruments to measure barriers, resources, self-efficacy for health behaviors, health promotion behaviors, and health-related QOL were completed at baseline, 2 months (after the classes), 5 months (after telephone follow-up), and at 8 months. Principal outcomes measures were health-promoting behaviors (scores on the Health Promoting Lifestyle Profile II) and QOL (scores on the Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36] scales).\n Hierarchical linear modeling techniques revealed a statistically significant group by time effect for self-efficacy for health behaviors, health-promoting behaviors, and the mental health and pain scales of the SF-36.\n These data provide initial support for the positive effects of wellness interventions to improve health behaviors and selected dimensions of QOL for women with MS.", "Cognitive problems in multiple sclerosis are common but any possible benefits of treatment remain uncertain. The aim of the study was to evaluate the benefits of providing a psychology service, including cognitive assessment and intervention, to patients with multiple sclerosis.\n The study was a single blind randomised controlled trial. A total of 240 patients with clinically definite, laboratory supported, or clinically probable multiple sclerosis were recruited from an multiple sclerosis management clinic and assessed on a brief screening battery. They were randomised into three groups. The control group received no further intervention. The assessment group received a detailed cognitive assessment, the result of which was fed back to staff involved in the patients' care. The treatment group received the same detailed cognitive assessment and a treatment programme designed to help reduce the impact of their cognitive problems. Patients were followed up 4 and 8 months later on the general health questionnaire (GHQ-28), extended activities of daily living scale, SF-36, everyday memory questionnaire, dysexecutive syndrome questionnaire, and memory aids questionnaire.\n The three groups were compared on the outcome measures at 4 and 8 months after recruitment. There were few significant differences between the groups and those that occurred favoured the control group. Overall, the results showed no effect of the interventions on mood, quality of life, subjective cognitive impairment or independence.\n The study failed to detect any significant effects of cognitive assessment or cognitive intervention in this cohort of people with multiple sclerosis.", "There has long been a belief that depression contributes to fatigue in multiple sclerosis (MS) although supporting data are minimal at best. Clinical guidelines for the treatment of fatigue include recommendations for the treatment of depression in the absence of clear empirical support. The goal of this study was to examine the effects of treatment for depression on fatigue in MS.\n Sixty patients with a relapsing form of MS and moderate to severe depression were randomly assigned to one of three validated 16-week treatments for depression: individual cognitive behavioral therapy, group psychotherapy, or sertraline. Assessments at baseline and treatment cessation included the primary outcome measure, fatigue assessment instrument (FAI), and Beck depression inventory (BDI).\n The total FAI and the global fatigue severity subscale were significantly reduced over the course of treatment (p values <.02). Other subscales did not change significantly. Secondary analyses showed change in global fatigue severity was associated with change in BDI (p =.03) but change in total FAI was only marginally related to change in BDI (p =.05). These relationships were due entirely to change in mood (p values <.02) and not to change in cognitive or vegetative symptoms (p values >.17).\n These findings suggest that treatment for depression is associated with reductions in the severity of fatigue symptoms, and that this relationship is due primarily to treatment related changes in mood.", "This study investigates the relationship between group psychotherapy and the psychologic adjustment of patients with a primary diagnosis of multiple sclerosis (MS). It was speculated that such a program would decrease both patient depression and anxiety, at the same time increasing self-concept and self-direction. Forty-one hospitalized MS patients were screened for mental status, then administered a test battery consisting of the Depression 30, IPAT Anxiety Scale, Nowicki-Strickland Internal-External Scale, and Rosenberg Self-Esteem Scale. Following this, patients were matched into triads on the basis of pretest scores. Each member of the triad was then randomly assigned to one of three groups: insight-oriented, current events, control (nontreatment). At the end of 50 group sessions, all patients were reassessed using the same test battery. Results were analyzed by means of analysis of covariance and the nonparametric Friedman test. Post-hoc procedures were performed with the following results: 1) the insight-oriented therapy group was significantly less depressed than both the current events group and the control group and 2) both the therapy and the current events groups were significantly more internally oriented than the control. Not only does group therapy per se seem to benefit the MS patient, but any supervised group involvement appears to improve significantly patient emotional state.", "This study examined the efficacy of an 8-week telephone-administered cognitive-behavioral therapy (CBT) for the treatment of depressive symptomatology in multiple sclerosis (MS) patients. The treatment, Coping with MS (CMS), included a patient workbook designed to structure the treatment, provide visual aids, and help with homework assignments. Thirty-two patients with MS, who scored at least 15 on the Profile of Mood States Depression-Dejection scale, were randomly assigned to either the telephone CMS or to a usual-care control (UCC) condition. Depressive symptomatology decreased significantly in the CMS condition compared with the UCC condition. Furthermore, adherence to interferon beta-1a, a disease-modifying medication for the treatment of MS, was significantly better at the 4-month follow-up among patients who received CMS as compared with those in the UCC condition.", "This study compared the efficacy of 3 16-week treatments for depression in 63 patients with multiple sclerosis (MS) and major depressive disorder (MDD): individual cognitive-behavioral therapy (CBT), supportive-expressive group therapy (SEG). and the antidepressant sertraline. Significant reductions were seen from pre- to posttreatment in all measures of depression. Intent-to-treat and completers analyses using the Beck Depression Inventory (BDI; A. T. Beck, C. H. Ward. M. Medelson. J. Mock, & J. Erbaugh, 1961) and MDD diagnosis found that CBT and sertraline were more effective than SEG at reducing depression. These results were largely supported by the BDI-18, which eliminates BDI items confounded with MS. However, the Hamilton Rating Scale for Depression (M. Hamilton, 1960) did not show consistent differences between treatments. Reasons for this inconsistency are discussed. These findings suggest that CBT or sertraline is more likely to be effective in treating MDD in MS compared with supportive group treatments.", "Multiple sclerosis (MS) is a chronic, often progressive neurologic disorder characterized by cerebral and spinal cord lesions. Patients with advanced MS often require continuous supervision in a long-term skilled nursing facility. Many of these patients experience clinical levels of depression. For this experiment, we randomly assigned MS patients living in a skilled nursing facility to either a control condition or an extended treatment protocol. The protocol consisted of assigning individual certified nursing assistants (CNAs) to each patient, in-service training for the CNAs, and the use of memory notebooks. All patients completed the short version of the Beck Depression Inventory and several measures of cognitive functioning at the start and end of the study. The results indicate statistically and clinically significant improvements in the depression of patients in the treatment but not in the control condition. These results led to recommendations for the treatment of MS patients living in long-term skilled nursing facilities and for additional research.", "The chronic and progressive nature of multiple sclerosis (MS) often excludes patients from neuropsychological treatment. At the Multiple Sclerosis Rehabilitation Hospital, Haslev, 40 patients with mild to moderate cognitive and behavioral impairment associated with MS were randomized to either specific cognitive treatment (20 pts) by direct training, compensatory strategies and neuropsychotherapy, or to non-specific, deliberately diffuse mental stimulation (20 pts). Treatment was for a mean of 46 days. The effects of treatment were evaluated by neuropsychological tests before treatment, immediately after treatment (short-term effects) and 6 months later (long-term effects). After short-term treatment, effects on cognitive measures were not convincing, but on the Beck Depression Inventory (BDI) the specific cognitive treatment group reported significantly less depression. After 6 months only this group showed an effect, since the visuo-spatial memory was improved. However, the depression ratings (BDI) were almost maintained from the short-term level. Interestingly, the non-specific treatment group rated themselves as significantly more depressed. Conclusively, it is worth while to offer specific neuropsychological treatment to MS patients with cognitive and behavioral dysfunction.", "The researchers studied the effectiveness of a nursing intervention in promoting adjustment and symptom management in individuals with multiple sclerosis (MS). This was a 4-year longitudinal study to determine whether the 4-week intensive outpatient program was effective in increasing adjustment to MS and if the treatment effect would last over time. A sample of 27 individuals with MS participated in the study. Treatment participants had significant improvements in symptom management at the 4-year follow up. This improvement was attributable to signficant improvements in sleep and fatigue levels. Although adjustment and self-efficacy scores improved in the treatment group over time, this improvement was not superior to the control group. This was anticipated because the behavioral changes would precede improvement in adjustment to life following the diagnosis of MS." ]	The diversity of psychological interventions identified indicates the many ways in which they can potentially help people with MS. No definite conclusions can be made from this review. However there is reasonable evidence that cognitive behavioural approaches are beneficial in the treatment of depression, and in helping people adjust to, and cope with, having MS.
CD008039	[ "11554954", "15482357", "16492236", "17563841", "15579612", "16618262", "8427430", "9825271" ]	[ "Efficacy of nonprescription doses of ibuprofen for treating migraine headache. a randomized controlled trial.", "Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks.", "Rofecoxib in the acute treatment of migraine: a randomized controlled clinical trial.", "Rizatriptan vs. ibuprofen in migraine: a randomised placebo-controlled trial.", "Rofecoxib versus ibuprofen for acute treatment of migraine: a randomised placebo controlled trial.", "Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute migraine: results from a multicenter, double-blind, randomized, parallel-group, single-dose, placebo-controlled study.", "The efficacy of metoclopramide in the treatment of migraine headache.", "Effectiveness of ibuprofen-arginine in the treatment of acute migraine attacks." ]	[ "To evaluate the efficacy and safety of ibuprofen, 200 mg and 400 mg, compared with placebo and each other for the treatment of pain of migraine headache.\n Migraine headache is a common illness with significant social and economic impact.\n Randomized, placebo-controlled, double-blind trial of 6 hours' treatment duration.\n Fifteen investigators at 17 private practice and referral centers in the United States participated in this study of 660 outpatient adults aged 18 to 84 years with migraine headache of moderate to severe intensity. Each patient was randomly assigned to a single dose of study medication: ibuprofen 200 mg (n = 216) or 400 mg (n = 223), or placebo (n = 221). The percentage of patients with a reduction in baseline headache intensity from severe or moderate to mild or none 2 hours after treatment and the headache pain intensity difference from baseline at 2 hours were the primary efficacy measures. Secondary outcomes included other measures of pain relief, severity differences from baseline for migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability, and percentage of patients with migraine-associated symptoms reduced to none.\n Significantly (P < or = .006) more patients treated with ibuprofen, 200 mg or 400 mg, reported mild to no pain after 2 hours (41.7% and 40.8%, respectively), compared with those treated with placebo (28.1%). The mean pain intensity difference from baseline measured at 2 hours was significantly (P < or = .001) greater for patients treated with ibuprofen 200 mg or 400 mg (0.68 and 0.65, respectively), compared with those treated with placebo (0.39). Statistically significant differences in favor of both doses of ibuprofen over placebo were observed for mean pain intensity difference at 1 hour after treatment. In patients with severe baseline pain intensity, ibuprofen, 400 mg, was significantly (P < or = .048) superior to placebo for the primary efficacy end points, while ibuprofen, 200 mg, was not. Ibuprofen, 200 mg and 400 mg, were statistically significantly more effective than placebo for all clinically important secondary pain relief outcomes. Mean severity changes of migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability at 2 and 6 hours were significantly (P < or = .03) in favor of both doses of ibuprofen over placebo, and results for the percentage of patients with symptoms reduced to none consistently, although less often statistically significant, favored ibuprofen. No statistically significant differences in adverse events were found among treatment groups.\n Ibuprofen at doses of 200 mg and 400 mg is an efficacious, cost-effective, well-tolerated, single-ingredient nonprescription treatment for pain of migraine headache. In addition, while not always statistically significant, ibuprofen provided a beneficial effect on associated symptoms of migraine including nausea, photophobia, phonophobia, and functional disability.", "Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.", "To investigate the efficacy, tolerability, and safety of rofecoxib and ibuprofen for acute migraine treatment.\n Rofecoxib was effective and well tolerated in a previous study of treatment of a single migraine attack. We sought to replicate these findings for a single attack and also study the clinical profile of rofecoxib in the acute treatment of multiple migraine attacks. Ibuprofen was included as a reference nonselective NSAID.\n Adult migraineurs (n = 783) treated one migraine attack with either rofecoxib (25 or 50 mg), ibuprofen 400 mg, or placebo in a randomized, double-blind study. Patients could elect to enroll in a 3-month double-blind extension phase.\n In the single-attack phase, headache relief at 2 hours postdose was reported by 59.4%, 62.2%, and 57.7% of patients who took rofecoxib 25 mg, rofecoxib 50 mg, and ibuprofen 400 mg, respectively, versus 30.5% for placebo (all P < .001 vs placebo). The active drugs were statistically superior to placebo on a variety of additional measures. In the extension phase, the mean percentage of patients' attacks with headache relief at 2 hours postdose was 61.8% for rofecoxib 25 mg, 65.4% for rofecoxib 50 mg, and 59.3% for ibuprofen 400 mg. The mean percentage of patients' attacks with 24-hour sustained headache relief was greater for rofecoxib 50 mg (52.0%) than for rofecoxib 25 mg (47.8%, P < .050) or ibuprofen (39.0%, P < .010). In the single-attack phase, the adverse event rate was higher for rofecoxib 50 mg (37.8%) than placebo (27.8%, P < .050); rates were similar to placebo for rofecoxib 25 mg (32.0%, n.s.) and ibuprofen 400 mg (28.1%, n.s.). In the extension phase, treatment groups had similar adverse event rates.\n Rofecoxib 25 and 50 mg and ibuprofen 400 mg were effective and generally well tolerated in the acute treatment of migraine.", "The objective of this study was to compare the efficacy of rizatriptan and ibuprofen in migraine. The study was a randomised placebo-controlled trial in a tertiary care teaching hospital. Migraine patients with <8 attacks/months were included. One hundred and fifty-five migraine patients were randomised to rizatriptan 10 mg (53), ibuprofen 400 mg (52) and placebo (50). Efficacy was assessed by headache relief, and headache freedom at 2 h and 24 h. Two-hour headache relief, was noted in 73% in rizatriptan, 53.8% in ibuprofen and 8% in placebo groups. Headache freedom was achieved in 37.7% in rizatriptan, 30.8% in ibuprofen and 2% in placebo groups. Rizatriptan was superior to ibuprofen and placebo in relieving headache at 2 h but not at 24 h. Side effects were noted in 9 patients in rizatriptan, 8 in ibuprofen and 3 in placebo, all of which were nonsignificant. Rizatriptan and ibuprofen are superior to placebo. Rizatriptan is superior to ibuprofen in relieving headache, associated symptoms and functional disability.", "Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long duration of action. Its role in migraine has not been systematically evaluated.\n To study the efficacy of rofecoxib in migraine.\n In a randomised placebo controlled trial rofecoxib 25 mg, ibuprofen 400 mg, and placebo were compared regarding their efficacy in relieving acute migraine attack. Migraine patients with 2-6 attacks per month were recruited. Headache severity, functional disability, and severity of associated symptoms were graded on a 0-3 scale. The primary endpoint was pain relief at two hours. Relief of associated symptoms and sustained pain relief for 24 hours were also noted.\n One hundred and twenty four patients were randomised into rofecoxib (42), ibuprofen (40), and placebo (42) groups. One hundred and one patients were followed up: 33 on rofecoxib, 35 ibuprofen, and 33 placebo. Patients' ages ranged from 16-62 (mean 31.4) years, and 83 were females. Pain relief at two hours was noted in 45.5% on rofecoxib, 55.6% on ibuprofen, and 9.1% in the placebo group. The associated symptoms at two hours were reduced in 39.4% on rofecoxib, 50% on ibuprofen, and 9.1% in the placebo group. Sustained 24 hour pain relief was noted in 36.4% on rofecoxib, 41% on ibuprofen, and 6.1% in the placebo group. In the ibuprofen group, five patients had abdominal pain but there were no side effects in those on rofecoxib or in the control group. Both rofecoxib and ibuprofen were significantly effective in relieving pain, associated symptoms at two hours, and in sustained pain relief. There was no significant difference between rofecoxib and ibuprofen in aborting acute migraine attacks.\n Both ibuprofen and rofecoxib were superior to placebo in aborting an acute migraine attack, and there was no significant difference in their efficacy in an acute migraine attack.", "Compare the effectiveness of a combination analgesic containing acetaminophen, aspirin, and caffeine to that of ibuprofen in the treatment of migraine.\n Multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study. A total of 1555 migraineurs were included in the analysis. No patients were excluded solely because of severity of symptoms or degree of disability. A single 2-tablet dose for each of the 3 treatment groups: a combination product containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg per tablet (AAC); ibuprofen 200 mg per tablet (IB); or matching placebo. The primary efficacy endpoint was the weighted sum of pain relief (PAR) scores at 2 hours postdose (TOTPAR2) and an important secondary endpoint was the time to onset of meaningful relief.\n There were 669 patients in the AAC group, 666 patients in the IB group, and 220 patients in the placebo group. The 3 treatment groups had similar demographic profiles, migraine histories, and baseline symptom profiles. While both active treatments were significantly better than placebo in relieving the pain and associated symptoms of migraine, AAC was superior to IB for TOTPAR2, as well as for PAR, time to onset of meaningful PAR, pain intensity reduction, headache response, and pain free. The mean TOTPAR2 scores for AAC, IB, and placebo were 2.7, 2.4, and 2.0, respectively (AAC vs. IB, P < .03). The median time to meaningful PAR for AAC was 20 minutes earlier than that of IB (P < .036).\n AAC and IB are safe, cost-effective treatments for migraine; AAC provides significantly superior efficacy and speed of onset compared with IB.", "By evaluating the efficacy of metoclopramide alone and in combination with ibuprofen versus placebos, this study was designed to both evaluate the efficacy of metoclopramide and elucidate its mechanism of action in the treatment of migraine headache.\n The study was conducted over a two-year period and was a randomized, double-blind, placebo-controlled study.\n An urban teaching hospital.\n Patients enrolled were at least 18 years old and had recurring headaches with one or more of the following characteristics: unilateral, preceded by neurologic symptoms, significant nausea and vomiting, or mood changes and photophobia.\n Ten milligrams of metoclopramide or an equal volume of IV normal saline was given and 600 mg of ibuprofen or identical-appearing placebo was given orally at time 0. Patients rated their pain and nausea at time 0, 30 minutes, and 60 minutes using visual-analog scales.\n The differences in pain and nausea scores for the metoclopramide + placebos group versus the other three groups were tested using exact nonparametric (Mann-Whitney) statistical procedures. The metoclopramide + placebos group had significantly better relief of pain compared with the placebos + ibuprofen and placebos + placebos groups. The metoclopramide + placebos group had significantly better relief of nausea than the ibuprofen + placebos group; nausea scores for the placebos + placebos group could not be analyzed due to excessive variance from the other groups at baseline. The differences between the metoclopramide + placebos group and the metoclopramide + ibuprofen group were not statistically significant with regard to either pain or nausea.\n Metoclopramide is efficacious in the treatment of both the pain and nausea of migraine headache. This is a direct action that is not dependent on the concomitant administration of another agent.", "The purpose of this study was to evaluate the effectiveness of a new formulation of ibuprofen (ibuprofen-arginine [IA]) in the treatment of migraine attacks. This is a faster absorbed formulation as compared with ibuprofen alone. The rapidity of action is considered to be a crucial factor in the treatment of migraine attacks. Forty migraine patients participated in this multicenter, double-blind, crossover, randomized, placebo-controlled trial. Each patient was treated with a single oral dose of IA 400 mg or placebo during two consecutive migraine attacks. The results confirm the efficacy of IA, with a significant (p < 0.05) improvement in pain relief at 30 min after treatment. A statistically significant (p < 0.001) reduction in pain intensity was observed at 1, 2, 4 and 6 h after treatment with ibuprofen as compared with placebo. IA was well tolerated and our data indicate that this new formulation of ibuprofen is valuable in the treatment of acute migraine attacks." ]	We found no new studies since the last version of this review. Ibuprofen is an effective treatment for acute migraine headaches, providing pain relief in about half of sufferers, but complete relief from pain and associated symptoms for only a minority. NNTs for all efficacy outcomes were better with 400 mg than 200 mg in comparisons with placebo, and soluble formulations provided more rapid relief. Adverse events were mostly mild and transient, occurring at the same rate as with placebo.
CD003287	[ "10526722", "11544612", "12757987", "10480767", "10321421", "12017407", "10834413", "11711322", "12873294", "11194244", "9686700", "10880892", "10480503", "10332684", "9183237", "9083709", "9000704", "11453959", "9167105", "12027927", "9444449", "15713351", "10332682", "12213353", "9250454", "15377436", "11476360", "11874927", "10784225", "12768948", "9032100", "9802741", "11553203", "12201618", "12873289", "9545126", "11694699", "12448933", "11131100", "11767232", "15523183", "11590992", "14557006", "14617222", "15111514", "9405901" ]	[ "Effect of the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. U.K. Lispro Study Group.", "Severe hypoglycaemia in patients with type 1 diabetes and impaired awareness of hypoglycaemia: a comparative study of insulin lispro and regular human insulin.", "Insulin lispro is as effective as regular insulin in optimising metabolic control and preserving beta-cell function at onset of type 1 diabetes mellitus.", "Improved postprandial glycemic control during treatment with Humalog Mix25, a novel protamine-based insulin lispro formulation. Humalog Mix25 Study Group.", "Improved postprandial blood glucose control and reduced nocturnal hypoglycemia during treatment with two novel insulin lispro-protamine formulations, insulin lispro mix25 and insulin lispro mix50. Mix50 Study Group.", "Comparison of insulin lispro with regular human insulin for the treatment of type 1 diabetes in adolescents.", "Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes.", "A comparison of insulin lispro and buffered regular human insulin administered via continuous subcutaneous insulin infusion pump.", "Insulin lispro: a potential role in preventing nocturnal hypoglycaemia in young children with diabetes mellitus.", "Efficacy, safety, and pump compatibility of insulin aspart used in continuous subcutaneous insulin infusion therapy in patients with type 1 diabetes.", "Use of the short-acting insulin analogue lispro in intensive treatment of type 1 diabetes mellitus: importance of appropriate replacement of basal insulin and time-interval injection-meal.", "Improved blood glucose variability, HbA1c insuman Infusat and less insulin requirement in IDDM patients using insulin lispro in CSII. The Swedish Multicenter Lispro Insulin Study.", "Metabolic and immunologic effects of insulin lispro in gestational diabetes.", "Contribution of postprandial versus interprandial blood glucose to HbA1c in type 1 diabetes on physiologic intensive therapy with lispro insulin at mealtime.", "Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group.", "Improved mealtime treatment of diabetes mellitus using an insulin analogue. Multicenter Insulin Lispro Study Group.", "Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Multicenter Insulin Lispro Study Group.", "Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF-I and IGFBP-1 in type 1 diabetes.", "Health-related quality-of-life results from multinational clinical trials of insulin lispro. Assessing benefits of a new diabetes therapy.", "Premixed insulin aspart 30 vs. premixed human insulin 30/70 twice daily: a randomized trial in Type 1 and Type 2 diabetic patients.", "Efficacy of insulin lispro in combination with NPH human insulin twice per day in patients with insulin-dependent or non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group.", "The effect of improved post-prandial blood glucose control on post-prandial metabolism and markers of vascular risk in people with Type 2 diabetes.", "Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. German Humalog-CSII Study Group.", "Insulin lispro therapy in pregnancies complicated by type 1 diabetes mellitus.", "Metabolic efficacy of preprandial administration of Lys(B28), Pro(B29) human insulin analog in IDDM patients. A comparison with human regular insulin during a three-meal test period.", "Effect of insulin lispro on glycaemic control in Chinese diabetic patients receiving twice-daily regimens of insulin.", "Lispro insulin in type 1 diabetic patients on a Mediterranean or normal diet: a randomized, cross-over comparative study with regular insulin.", "Comparison of insulin aspart with buffered regular insulin and insulin lispro in continuous subcutaneous insulin infusion: a randomized study in type 1 diabetes.", "A randomized, controlled trial comparing insulin lispro with human soluble insulin in patients with Type 1 diabetes on intensified insulin therapy. The UK Trial Group.", "Humalog Mix25 improves 24-hour plasma glucose profiles compared with the human insulin mixture 30/70 in patients with type 2 diabetes mellitus.", "Insulin lispro in CSII: results of a double-blind crossover study.", "Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1 diabetic patients. UK Insulin Aspart Study Group.", "Post-prandial insulin lispro vs. human regular insulin in prepubertal children with Type 1 diabetes mellitus.", "Effects of a fixed mixture of 25% insulin lispro and 75% NPL on plasma glucose during and after moderate physical exercise in patients with type 2 diabetes.", "Effect of the rapid-acting insulin analogue insulin aspart on quality of life and treatment satisfaction in patients with Type 1 diabetes.", "Human insulin analogue [LYS(B28), PRO(B29)]: the ideal pump insulin?", "Insulin lispro lowers postprandial glucose in prepubertal children with diabetes.", "Insulin lispro improves postprandial glucose control in patients with diabetes mellitus.", "Insulin aspart vs. human insulin in the management of long-term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trial.", "A comparative study of insulin lispro and human regular insulin in patients with type 2 diabetes mellitus and secondary failure of oral hypoglycemic agents.", "Special management of insulin lispro in continuous subcutaneous insulin infusion in young diabetic children: a randomized cross-over study.", "Preprandial combination of lispro and NPH insulin improves overall blood glucose control in type 1 diabetic patients: a multicenter randomized crossover trial.", "Maternal metabolic control and perinatal outcome in women with gestational diabetes treated with regular or lispro insulin: comparison with non-diabetic pregnant women.", "Comparison of additional metformin or NPH insulin to mealtime insulin lispro therapy with mealtime human insulin therapy in secondary OAD failure.", "A direct efficacy and safety comparison of insulin aspart, human soluble insulin, and human premix insulin (70/30) in patients with type 2 diabetes.", "Reduced frequency of severe hypoglycemia and coma in well-controlled IDDM patients treated with insulin lispro. The Benelux-UK Insulin Lispro Study Group." ]	[ "To measure the effectiveness of insulin lispro, a fast-acting insulin analog, in reducing hypoglycemic episodes when used in a basal bolus regimen by patients with type 1 diabetes using intensive insulin therapy.\n In 11 diabetes outpatient clinics in the U.K., 165 subjects with type 1 diabetes were enrolled in a randomized crossover open-label study with a 2-month run-in period and then treated with a basal bolus regimen. Patients used human NPH insulin at night with either premeal insulin lispro for 4 months followed by human regular insulin for another 4 months or human regular insulin for 4 months followed by insulin lispro for another 4 months. The main outcome measures were the number of hypoglycemic episodes during both treatments and HbA1c level.\n A total of 135 patients were randomized, with 68 receiving insulin lispro and 67 receiving human regular insulin for the first 4 months. The data for the first 4 months of treatment only were compared as two independent groups because of a period effect and a treatment-period interaction. Glycemic control was equally tight during treatment with human regular insulin (HbA1c, 6.2 +/- 0.8%) and insulin lispro (6.0 +/- 0.9%). A total of 1,156 hypoglycemic episodes occurred during treatment with human regular insulin compared with 775 hypoglycemic episodes that occurred during treatment with insulin lispro (P = 0.04). This difference was chiefly because of a reduced number of nocturnal episodes (181 vs. 52, P = 0.001) in the insulin lispro group.\n The use of a fast-acting insulin analog, insulin lispro, as part of a basal bolus regimen reduces nocturnal hypoglycemia in patients with type 1 diabetes who maintain tight glycemic control during intensive insulin therapy.", "To assess the potential of insulin lispro to limit the frequency of severe hypoglycaemia without compromising glycaemic control in a cohort of patients with type 1 diabetes who are at a high risk of severe hypoglycemia. Research design and methods An open-label, randomised, 12-month comparative crossover study of insulin lispro and regular human insulin was performed in 33 patients with type 1 diabetes with impaired hypoglycaemia awareness. The efficacy of each treatment was evaluated by glycaemic control (HbA(1c)), eight-point home blood glucose profiles, and the frequency and severity of hypoglycaemic episodes and quality of life.\n Eighteen (55%) patients experienced one or more episodes of severe hypoglycaemia in the 48 weeks of study. There was a trend to a lower incidence of severe hypoglycaemia during treatment with insulin lispro in comparison with regular human insulin (55 vs 84 episodes, p=0.087). This resulted principally from a 47% lower incidence of nocturnal severe hypoglycaemia with insulin lispro (25 vs 47 episodes, p=0.11). The lower frequency of severe hypoglycaemia associated with insulin lispro was not explained by differences in glycated haemoglobin between insulin treatments (HbA(1c) 9.1% insulin lispro vs 9.3% regular human insulin).\n In individuals with type 1 diabetes, who have impaired awareness of hypoglycaemia, treatment with insulin lispro may be associated with a lower incidence of severe hypoglycaemia manifested predominantly through less frequent nocturnal episodes. Insulin lispro may have a beneficial role in the management of patients with diabetes at risk of severe hypoglycaemia, although a larger study is required to confirm these findings.\n Copyright 2001 John Wiley & Sons, Ltd.", "The aim of the study was to examine the effects of intensive insulin therapy using lispro on metabolic control, immunogenicity and beta-cell function of newly diagnosed type 1 diabetic subjects in comparison with intensive insulin therapy using regular insulin. An open study was conducted in 45 newly diagnosed type 1 diabetic subjects. Patients were randomly assigned to intensive insulin therapy using insulin lispro (lispro) (lispro, n=22; 22.8 years) or intensive insulin therapy using regular insulin (regular) (regular, n=23; 24.4 years): three to five injections of subcutaneous rapid-acting insulin before meals and Neutral Protamine Hagedorn (NPH) before dinner/bed-time. GAD, IA2, insulin antibodies, basal and stimulated plasma C-peptide and HbA(1c) were measured initially and at months 1, 4, 8 and 12. Daily blood glucose profiles tended to be lower in the lispro group, particularly values after breakfast, without reaching statistical significance. There were no differences in terms of HbA(1c) throughout the study. The proportion of subjects achieving an HbA(1c)<6% at the end of the study was similar in both groups (regular 73.9%, lispro 68.0%). The number of mild hypoglycemic episodes tended to be lower with lispro, but not significantly. beta-Cell function was not significantly different in both groups. During follow-up there were no differences in antibodies, including IAAb. In summary, insulin lispro used in intensive insulin therapy is as effective as regular insulin in optimizing metabolic control and preserving beta-cell function at diagnosis of type 1 diabetes.", "Humalog Mix25 is a manufactured premixed insulin formulation containing insulin lispro and a novel insulin lispro-protamine formulation (NPL) in a ratio of 25:75%. The objective of this study was to compare Humalog Mix25 to human insulin 30/70 (30% regular insulin/70% NPH) with respect to glycemic control.\n Humalog Mix25 was compared with human insulin 30/70 in 89 individuals with type 2 diabetes during a 6-month randomized open-label two-period crossover study. Each insulin was administered twice daily, before the morning and evening meals. Information regarding self-monitored blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG < or = 3.0 mmol/l), insulin dose, and HbA1c was collected.\n Treatment with Humalog Mix25 resulted in better postprandial glycemic control after the morning and evening meals compared with treatment with human insulin 30/70. Overall glycemic control and the incidence of hypoglycemia were comparable between the treatments.\n In comparison to treatment with human insulin 30/70, twice daily administration of Humalog Mix25 resulted in improved postprandial glycemic control, similar overall glycemic control, and the convenience of dosing immediately before meals.", "The objective of this 6-month, open-label, randomized, two-period crossover study was to compare glycemic control when patients were treated with (1) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation, neutral protamine lispro (NPL), and (2) 2 manufactured premixed human insulin formulations, human insulin 50/50 and human insulin 30/70. One hundred individuals, 37 with type 1 diabetes mellitus (12 females, 25 males; mean age, 39.4 years; mean body mass index [BMI], 24.8; mean duration of diabetes, 12.9 years) and 63 with type 2 diabetes mellitus (33 females, 30 males; mean age, 59.0 years; mean BMI, 28.4; mean duration of diabetes, 12.6 years), were treated with insulin lispro mixtures. Insulin lispro Mix50 (50% insulin lispro/50% NPL) and human insulin 50/50 (50% regular insulin/50% neutral protamine Hagedorn [NPH] insulin) were administered before breakfast; insulin lispro Mix25 (25% insulin lispro/75% NPL) and human insulin 30/70 (30% regular insulin/70% NPH) were administered before dinner. Blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG <3.0 mmol/L), insulin dose and timing of dose before meals, and hemoglobin A1c were measured. Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups. However, compared with human insulin mixtures, twice-daily administration of insulin lispro mixtures resulted in improved postprandial glycemic control, similar overall glycemic control, and less nocturnal hypoglycemia, as well as offering the convenience of dosing closer to meals.", "Although insulin lispro (insulin LP) has been shown to improve postprandial blood glucose (BG) control and reduce hypoglycemic episodes in adult patients with type I diabetes, there appear to have been few clinical studies focusing on its use in adolescents.\n This study compared the effects of insulin LP with those of regular human insulin (insulin R) on postprandial BG control and hypoglycemia in adolescents with type diabetes.\n In this crossover, open-label study, adolescents between the ages of 9 and 18 years who had reached Tanner stage II puberty were randomized to receive either insulin LP immediately before meals or insulin R 30 to 45 minutes before meals, in addition to daily intermediate-acting insulin. After 4 months, patients were switched to the alternate treatment sequence. Eight-point BG profiles, hypoglycemia rate, and glycosylated hemoglobin (HbA1c) were measured at baseline and end point.\n Four hundred eighty-one adolescents participated in the study at 53 investigative sites in 15 countries; 463 were randomized to treatment (228 insulin LP, 235 insulin R), and 457 completed the study. Insulin LP given before breakfast resulted in significantly lower mean (+/-SD) 2-hour postprandial BG levels compared with insulin R (9.7 +/- 4.0 mmol/L vs 10.6 +/- 4.3 mmol/L, respectively; P < 0.001). Insulin LP given before dinner resulted in significantly lower 2-hour postprandial BG levels compared with insulin R (8.6 +/- 3.5 mmol/L vs 9.3 +/- 3.7 mmol/L; P = 0.003). No differences were seen between treatments in 2-hour postprandial BG levels after the midday meal. Mean baseline HbA1c values were similar between sequence groups, and no between-group difference in HbA1c was observed at end point (insulin LP, 8.69% +/- 1.52%; insulin R, 8.70% +/- 1.65%). Treatment with insulin LP resulted in a significantly lower incidence of hypoglycemic episodes per patient per 30 days compared with insulin R (4.02 +/- 4.5 vs 4.37 +/- 4.5, respectively; P = 0.023) and significantly fewer hypoglycemic episodes between midnight and 6 AM (1.0 +/- 1.9 vs 1.7 +/- 2.6; P < 0.001).\n In adolescents with type 1 diabetes, insulin LP significantly improved postprandial glycemic control and reduced episodes of nocturnal hypoglycemia compared with insulin R. Insulin LP was well tolerated and effective as part of an intensified insulin regimen in this study population.", "To compare long-term glycemic control and safety of using insulin aspart (IAsp) with that of regular human insulin (HI).\n This was a multicenter randomized open-label 6-month study (882 subjects) with a 6-month extension period (714 subjects) that enrolled subjects with type 1 diabetes. Subjects administered IAsp immediately before meals or regular HI 30 min before meals; basal NPH insulin was taken as a single bedtime dose in the majority of subjects. Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals.\n Mean postprandial blood glucose levels (mg/dl +/- SEM) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast (156 +/- 3.4 vs. 185 +/- 4.7), lunch (137 +/- 3.1 vs. 162 +/- 4.1), and dinner (153 +/- 3.1 vs. 168 +/- 4.1), when assessed after 6 months of treatment. Mean HbA1c values (% +/- SEM) were slightly, but significantly, lower for the IAsp group (7.78% +/- 0.03) than for the regular HI group (7.93% +/- 0.05, P = 0.005) at 6 months. Similar postprandial blood glucose and HbA1c values were observed at 12 months. Adverse events and overall hypoglycemic episodes were similar for both treatment groups.\n Postprandial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment. The improvement was not obtained at an increased risk of hypoglycemia. HbA1c was slightly, but significantly, lower for IAsp compared with HI at 6 and 12 months.", "This study compared glycemic control achieved with insulin lispro or buffered regular human insulin in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) using an external insulin pump. In this 24-week multicenter, randomized, two-way crossover, open-label trial, 58 patients on CSII with adequate glycemic control received either insulin lispro or buffered regular human insulin for 12 weeks, followed by the alternate treatment for another 12 weeks. Efficacy and safety measures included hemoglobin A(1c) (HbA(1c)) at baseline and endpoint, home blood glucose monitoring, hypoglycemia, and frequency of pump catheter occlusion. Patients consumed a standard test meal on three occasions, with determinations of fasting, 1- and 2-h postprandial glucose values. Insulin lispro use was associated with a significantly lower HbA(1c) than was buffered regular human insulin (7.41+/-0.97 vs. 7.65+/-0.85 mmol/l; P=.004). Fasting serum glucose values before the test meal were similar between the two therapies. The 1-h (11.16+/-4.29 vs. 13.20+/-4.68 mmol/l; P=.012) and 2-h (9.64+/-4.10 vs. 12.53+/-4.64 mmol/l; P=.001) postprandial glucose concentrations were significantly lower during treatment with insulin lispro. No differences between treatments were observed in basal or bolus insulin doses, weight gain, or the incidence and rate of hypoglycemia, hyperglycemia, or pump occlusions. When used in external pumps, insulin lispro provides better glycemic control than buffered regular human insulin with a similar adverse event profile.", "The long duration of action of soluble insulin given in the evening could contribute to the high prevalence of nocturnal hypoglycaemia seen in young children with Type 1 diabetes mellitus (T1DM). We examined whether replacing soluble insulin with insulin lispro reduced this risk in children on a three times daily insulin regimen.\n Open crossover study comparing insulin lispro vs. soluble insulin in 23 (16 boys) prepubertal children (age 7-11 years) with T1DM on three injections/day; long-acting isophane insulin remained identical. At the end of each 4-month treatment arm, an overnight 15-min venous sampled blood glucose profile was performed.\n Despite similar blood glucose levels pre-evening meal (lispro vs. soluble: mean +/- se 6.5 +/- 1.0 vs. 7.1 +/- 1.1 mmol/l, P = 0.5), post-meal (18.00-22.00 h) blood glucose levels were lower on insulin lispro (area under curve 138 +/- 12 vs. 170 +/- 13 mmol min-1 l-1, P = 0.03). In contrast, in the early night (22.00-04.00 h) the prevalence of low blood glucose levels (< 3.5 mmol/l) was lower on lispro (8% of blood glucose levels) than on soluble insulin (13%, P = 0.01). In the early morning (04.00-07.00 h) mean blood glucose and prevalence of low levels were no different between the two treatment groups, and fasting (07.00 h) blood glucose levels were similar (6.1 +/- 0.8 vs. 6.3 +/- 0.9 mmol/l, P = 0.8). At the end of each treatment arm there were no differences in HbA1c (lispro vs. soluble 8.6% vs. 8.4%, P = 0.3), or in insulin doses (mean, range 0.97, 0.68-1.26 vs. 0.96, 0.53-1.22 U/kg per day, P = 0.2).\n The shorter duration of action of insulin lispro given before the evening meal may reduce the prevalence of early nocturnal hypoglycaemia without compromising HbA1c in young children with T1DM.", "The purpose of this study was to compare the efficacy, safety and pump compatibility of insulin aspart (a rapid-acting insulin analog) and buffered regular human insulin in patients with type 1 diabetes undergoing continuous subcutaneous insulin infusion (CSII) therapy.\n This was a single-center randomized open-label study Patients received CSII therapy with insulin aspart (n = 19) or buffered regular human insulin (n = 10) for 7 weeks. Bolus doses of insulin aspart were administered immediately before meals and buffered regular human insulin 30 min before meals.\n Insulin aspart and buffered regular human insulin were both effective in controlling average daily blood glucose levels (8.2 +/- 1.9 and 8.5 +/- 2.1 mmol/l, respectively) (mean +/- SD) and maintaining serum fructosamine (343 +/- 25.7 and 336 +/- 27.4 micromol/l) and HbA1c (6.9 +/- 0.6 and 7.1 +/- 0.6%) levels. Possible obstructions and set leakages were infrequently reported in both groups. Similar numbers of patients experienced hypoglycemia (blood glucose <2.5 mmol/l): 14 (74%) insulin aspart patients versus 6 (60%) buffered regular human insulin patients. Patients receiving insulin aspart had fewer hypoglycemic events per patient (2.9) than those patients receiving buffered regular human insulin (6.2). There were no differences between the two insulins in the occurrence of hyperglycemic events (blood glucose >19 mmol/l) or in the number and type of adverse events.\n Insulin aspart and buffered regular human insulin were effective and well tolerated and provided similar pump compatibility when used in CSII therapy.", "To establish whether lispro may be a suitable short-acting insulin preparation for meals in intensive treatment of Type 1 diabetes mellitus (DM) in patients already in chronic good glycaemic control with conventional insulins, 69 patients on intensive therapy (4 daily s.c. insulin injections, soluble at each meal, NPH at bedtime, HbA1c <7.5%) were studied with an open, cross-over design for two periods of 3 months each (lispro or soluble). The % HbA1c and frequency of hypoglycaemia were assessed under four different conditions (Groups I-IV). Lispro was always injected at mealtime, soluble 10-40 min prior to meals (with the exception of Group IV). Bedtime NPH was continued with both treatments. When lispro replaced soluble with no increase in number of daily NPH injections (Group I, n = 15), HbA1c was no different (p = NS), but frequency of hypoglycaemia was greater (p < 0.05). When NPH was given 3-4 times daily, lispro (Group II, n = 18), but not soluble (Group III, n = 12) decreased HbA1c by 0.35 +/- 0.25% with no increase in hypoglycaemia. When soluble was injected at mealtimes, HbA1c increased by 0.18 +/- 0.15% and hypoglycaemia was more frequent than when soluble was injected 10-40 min prior to meals (Group IV, n = 24) (p < 0.05). It is concluded that in intensive management of Type 1 DM, lispro is superior to soluble in terms of reduction of % HbA1c and frequency of hypoglycaemia, especially for those patients who do not use a time interval between insulin injection and meal. However, these goals cannot be achieved without optimization of basal insulin.", "The aim of the study was to compare lispro (LP) and Insuman(R) (I) insulin in continuous subcutaneous insulin infusion (CSII) therapy with respect to blood glucose control as expressed by the standard deviation of blood glucose (SD(BG) ) and HbA(1c) and to monitor the well-being (WBQ) and treatment satisfaction (DTSQ) parameters during such treatment. Forty-one IDDM patients who had used CSII for at least 6 months participated in an open-label, randomized, cross-over, multicenter study for 4 months (2 months LP and 2 months I or vice versa). Boluses with LP were given 5 min before each meal and with I 30 min before each meal. During LP administration compared with I, the SD(BG) of all blood glucose values (3.6 mmol/l vs. 3.9 mmol/l, p=0.012), as well as the SD(BG) of the postprandial, blood glucose values (3.6 mmol/l vs. 4.0 mmol/l, p=0.006), were significantly reduced. The HbA(1c) was significantly lower during LP administration (7.4% vs. 7.6%, p=0.047). The incidence of hypoglycemic events per 30 days (capillary blood glucose<3.0 mmol/l and/or symptoms) did not significantly differ between LP and I (9.7 vs. 8.0 per month, p=0.23). The total amount of daily insulin was slightly but significantly lower with LP, compared to I (38.0 IU vs. 40.3 IU, p=0.004). There was no treatment effects of LP compared to I concerning WBQ and DTSQ. It is concluded that in CSII therapy LP is superior to I with respect to the stability of blood glucose control, a lower HbA(1c), a less insulin requirement without increasing the frequency of hypoglycemia.", "To compare the immunologic response to insulin lispro with that to regular human insulin, thereby assuring its safety for use in women with gestational diabetes, and to verify that it is effective.\n We compared the metabolic and immunologic effects of insulin lispro and regular human insulin in 42 women >18 years of age diagnosed with gestational diabetes by oral glucose tolerance testing at 14-32 weeks of gestation. Patients were randomized to receive regular human insulin or insulin lispro before consuming a test meal. Serum insulin, blood glucose, and C-peptide concentrations were measured. Throughout the remainder of gestation, patients received premeal insulin lispro or regular human insulin combined with basal insulin and performed blood glucose self-monitoring before and after each meal. Insulin antibodies and HbA1c were determined at enrollment and 6 weeks later. In addition, 10 patients received continuous intravenous insulin (4 lispro, 6 regular human insulin) and dextrose infusions intrapartum to assess placental insulin transfer.\n Anti-insulin antibody levels were similar in the two groups. Insulin lispro was not detectable in the cord blood. During a meal test, areas under the curve for glucose, insulin, and C-peptide were significantly lower in the lispro group. Mean fasting and postprandial glucose concentrations and end point HbA1c were similar in the two groups. The lispro group demonstrated fewer hypoglycemic episodes (symptoms and blood glucose concentrations <55 mg/dl). No fetal or neonatal abnormalities were noted in either treatment group.\n Insulin lispro may be considered a treatment option for women with gestational diabetes.", "To quantitate the contribution of postprandial blood glucose, which improves with the short-acting insulin analog lispro [Lys(B28),Pro(B29)] in type 1 diabetes, to the overall 24-h blood glucose concentration and the long-term HbA1c concentration under conditions of different postabsorptive blood glucose.\n A total of 24 type 1 diabetic patients on long-term intensive therapy with premeal human regular insulin (Hum-R) and bedtime NPH were randomly assigned to a continuation of Hum-R (group 1, n = 8), lispro (group 2, n = 8), or lispro + NPH (in variable proportions) administered at mealtime (group 3, n = 8) for 3 months, NPH administered at bedtime was continued in all three groups. Data from home blood glucose monitoring were collected, and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postprandial glucose curve (3.5 h after breakfast, 3.5 h after lunch, and 3.0 h after dinner for a total of 10.0 h) and the postabsorptive blood glucose curve (the remaining 14.0 h out of 24.0 h) (AUC). Eight nondiabetic subjects were also studied.\n The substitution of Hum-R with lispro (group 2) resulted in lower postprandial blood glucose, but greater postabsorptive blood glucose (P < 0.05 vs. group 1). The postprandial blood glucose AUC was lower (161 +/- 19 vs. 167 +/- 20 mg.100 ml-1.h-1), but the postabsorptive blood glucose AUC was greater (155 +/- 22 vs. 142 +/- 19 mg.100 ml-1.h-1) (P < 0.05). Therefore, the 24-h blood glucose AUC was no different (NS). Consequently, HbA1c was no different (NS). This occurred because in group 2, mealtime lispro resulted in normal prandial plasma insulin, but also resulted in lower interprandial concentration (P < 0.05 vs. group 1). When NPH was added to lispro (30% at breakfast, 40% at lunch, 10% at dinner) in group 3, postabsorptive plasma insulin was similar to group 1 (NS), in group 3, the postprandial blood glucose AUC (153 +/- 17 mg.100 ml-1.h-1) was lower and the postabsorptive blood glucose AUC was no different, as compared with group 1 (NS). Therefore, the 24-h blood glucose AUC was lower (147 +/- 17 vs. 155 +/- 21 and 158 +/- 20 mg.100 ml-1.h-1), and HbA1c was lower (6.41 +/- 0.12 vs. 6.84 +/- 0.2 and 6.96 +/- 0.2% (groups 3, 1, and 2 respectively, P < 0.05). Frequency of hypoglycemia was greater in group 2 (P < 0.05), but not in group 3 (NS) vs. group 1.", "Insulin lispro is an insulin analog that was recently developed particularly for a mealtime therapy. It has a fast absorption rate and short duration of action. The efficacy of insulin lispro in the clinical therapy of patients with non-insulin-dependent diabetes mellitus (NIDDM) has not been tested.\n To compare insulin lispro and human regular insulin in the mealtime treatment of patients with NIDDM.\n A 6-month, randomized, multinational (16 countries), multicenter (80 sites) clinical trial with an open-label, crossover design was performed in 722 patients with NIDDM. Insulin lispro was injected immediately before and human regular insulin 30 to 45 minutes before the meal.\n Throughout the study, the postprandial rise in serum glucose levels was significantly lower during insulin lispro than human regular insulin treatment. At end point the rise (mean +/- SEM) in serum glucose levels was 30% lower at 1 hour (2.6 +/- 0.1 mmol/L [46.8 +/- 1.8 mg/ dL] for lispro vs 3.7 +/- 0.1 mmol/L [66.6 +/- 1.8 mg/dL] for human regular insulin) and 53% lower 2 hours after the test meal (1.4 +/- 0.1 mmol/L [25.2 +/- 1.8 mg/dL] for lispro vs 3.0 +/- 0.1 mmol/L [54.0 +/- 1.8 mg/dL] for human regular insulin) with insulin lispro compared with human regular insulin therapy (P < .001 for both intervals). During insulin lispro therapy the rate of hypoglycemia overall (P = .01) and overnight (P < .001) was lower and the number of asymptomatic hypoglycemic episodes was smaller (P = .03) than during human regular insulin therapy. Associated with a similar 13% increase (P < .001) in the total daily insulin dose, the glycosylated hemoglobin level decreased (P < .001) equally in both treatment groups. Serum lipid and lipoprotein levels remained unchanged. There were no differences in the adverse events between the 2 treatment groups.\n Compared with human regular insulin therapy, mealtime therapy with insulin lispro reduced postprandial hyperglycemia and may decrease the rate of mild hypoglycemic episodes in patients with NIDDM.", "The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms. The insulin analogue insulin lispro has a weak self-association and a fast absorption rate. We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus. A 12-month study was performed in 336 patients with insulin-dependent diabetes mellitus (IDDM) and 295 patients with non-insulin-dependent diabetes mellitus (NIDDM). The patients were randomized to inject either regular human insulin 30 to 45 minutes before eating, or insulin lispro immediately before each meal, in addition to basal insulin. The postprandial rise in serum glucose was lower in patients receiving insulin lispro than in those receiving regular human insulin therapy. At end point the increment was significantly lower at 1 hour (35%) and at 2 hours (64%) after the meal in IDDM patients; in NIDDM patients, the increment was nonsignificantly lower at 1 hour (19%) and significantly lower at 2 hours (48%). IDDM patients receiving insulin lispro achieved significantly lower glycated hemoglobin (HbA1c) levels in patients receiving regular human insulin (8.1% vs 8.3%). In NIDDM patients, HbA1c levels decreased equally in both treatment groups. Due to its fast absorption rate, insulin lispro improves postprandial control in diabetes. Insulin lispro can be considered one step toward optimal insulin therapy and improved patient convenience.", "Insulin lispro, an insulin analog recently developed particularly for mealtime therapy, has a fast absorption rate and a short duration of action. We compared insulin lispro and regular human insulin in the mealtime treatment of 1,008 patients with IDDM. The study was a 6-month randomized multinational (17 countries) and multicenter (102 investigators) clinical trial performed with an open-label crossover design. Insulin lispro was injected immediately before the meal, and regular human insulin was injected 30-45 min before the meal. Throughout the study, the postprandial rise in serum glucose was significantly lower during insulin lispro therapy. At the endpoint, the postprandial rise in serum glucose was reduced at 1 h by 1.3 mmol/l and at 2 h by 2.0 mmol/l in patients treated with insulin lispro (P < 0.001). The rate of hypoglycemia was 12% less with insulin lispro (6.4 +/- 0.2 vs. 7.2 +/- 0.3 episodes/30 days, P < 0.001), independent of basal insulin regimen or HbA1c level. The reduction was observed equally in episodes with and without symptoms. When the total number of episodes for each patient was analyzed according to the time of occurrence, the number of hypoglycemic episodes was less with insulin lispro than with regular human insulin therapy during three of four quarters of the day (P < 0.001). The largest relative improvement was observed at night. In conclusion, insulin lispro improves postprandial control, reduces hypoglycemic episodes, and improves patient convenience, compared with regular human insulin, in IDDM patients.", "IGF-I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF-I and IGFBP-1 than that seen during treatment with conventional human insulin (regular insulin).\n Twelve patients with type 1 diabetes, age 47.8 +/- 2.4 years (mean +/- SEM), body mass index 26.5 +/- 1.0 kg/m2, diabetes duration 30.5 +/- 3.2 years participated in this open label randomized cross-over study. IGF-I and IGFBP-1 levels were measured at the end of 6 weeks treatment with each insulin being administered by a continuous subcutaneous insulin infusion. IGF-I was measured fasting while IGFBP-1, free insulin and blood glucose were measured fasting and repeatedly after a morning meal preceded by an insulin bolus dose.\n Lispro gave a marked insulin peak of 135 +/- 20 pmol/l 50 minutes after injection. After an initial rapid rise, human regular insulin reached a plateau of approximately 50 pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h was more than twice as large on lispro as on regular insulin (P = 0.01). Plasma IGF-I concentration was 78.8 +/- 10.9 microg/l on lispro and 82.3 +/- 10.5 microg/l on human regular insulin (not significant). AUC for IGFBP-1 did not show a significant difference even when divided from 0710 h to 0910 h and from 0930 h to 1430 h. Blood glucose AUC after administration of the bolus was significantly lower during treatment with lispro (P = 0.006) but glycosylated haemoglobin (HbA1c) was 6.4 +/- 0.2% on both therapies.\n Our results indicate that the effect of lispro on IGF-I and IGFBP-1 in patients with type 1 diabetes does not differ from that of human regular insulin.", "To compare health-related quality of life (HRQOL) in patients with diabetes receiving insulin lispro with patients receiving regular human insulin (Humulin R).\n We performed two randomized comparative studies over a 6-month period (3 months per treatment). Primary analyses used crossover baseline to 3-month changes in HRQOL scores. Ninety-three principal investigators in Canada, France, Germany, and the U.S. participated in these studies. One HRQOL crossover study included 468 patients with type I diabetes; the other HRQOL crossover study included 474 patients with type II diabetes. In both studies, patients were taking insulin at least 2 months before enrollment. Primary outcomes included two generic HRQOL domains, energy/fatigue and health distress, and two diabetes-specific domains, treatment satisfaction and treatment flexibility. Thirty secondary outcomes included both generic and diabetes-specific measures. Secondary outcome domains were controlled for multiplicity in the analyses.\n Primary analyses showed that treatment satisfaction scores (P < 0.001) and treatment flexibility scores (P = 0.001) were higher for insulin lispro in type I diabetic patients. No other significant treatment differences were detected using the data from these 6-month crossover studies.\n Treatment satisfaction and treatment flexibility were significantly improved in patients with type I diabetes using insulin lispro. Other HRQOL findings were comparable for insulin lispro and regular human insulin. Insulin lispro appears to have a measurable impact on lifestyle benefits in patients with type I diabetes, as demonstrated by increased treatment satisfaction and treatment flexibility.", "To compare the efficacy and safety of premixed insulin aspart (30% free and 70% protamine-bound, BIAsp 30) with human insulin premix (BHI 30) used in a twice-daily injection regimen in people with Type 1 and Type 2 diabetes.\n People with Type 1 and Type 2 diabetes (n = 294) using twice-daily insulin were randomized to a 12-week open-label comparison of BIAsp 30 and BHI 30. Efficacy was assessed by analysis of variance of 12-week data, adjusted for baseline level.\n BIAsp 30 was as effective as BHI 30 based on the primary efficacy measure, HbA1c, mean difference -0.01 (90% confidence interval (CI) -0.14; 0.12) %Hb. Meal-time self-measured blood glucose increment averaged over the three main meals was significantly lower in the BIAsp 30 group than in the BHI 30 group (-0.68 (-1.20; -0.16) mmol/l; P < 0.02). Significant improvements were observed after breakfast, before lunch, after dinner and at bedtime (P < 0.02-0.05), with blood glucose around 1.0 mmol/l lower in the BIAsp 30 group. The number of major hypoglycaemic episodes with BIAsp 30 was half that with BHI 30. However, the overall risk of both minor and major hypoglycaemia did not differ significantly between treatments.\n Post-prandial glycaemic control was significantly improved, without increasing the risk of hypoglycaemia, and overall control was similar when people with Type 1 and Type 2 diabetes were treated on a twice-daily regimen with immediate premeal injections of BIAsp 30 compared with BHI 30.", "A common treatment regimen for patients with either insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) is a combination of rapid-acting insulin and intermediate-acting insulin administered twice each day. It is usually recommended that regular human insulin be injected 30 to 45 minutes before a meal. In practice, patients often inject regular human insulin closer to mealtime, causing a higher post-prandial serum glucose level and an increased potential for hypoglycemia in the postabsorptive period. Insulin lispro, a rapid-acting insulin analogue, is best injected just before a meal because of its more rapid absorption and shorter duration of action. In 707 randomized patients, 379 with IDDM and 328 with NIDDM, we studied the effect of twice-daily insulin lispro or regular human insulin in combination with NPH human insulin (isophane insulin) on premeal, 2-hour postprandial, and bedtime glycemic control. Assessments were based on the results of a seven-point blood glucose profile, the insulin dose (by formulation and time of administration), the incidence and frequency of hypoglycemic episodes, and the glycated hemoglobin value. Treatment with insulin lispro resulted in lower postprandial glucose levels and smaller increases in glucose level after the morning and evening meals compared with treatment with regular human insulin. Overall glycemic control, frequency of hypoglycemic events, and total insulin dose were not different between the two groups. Insulin lispro in combination with NPH human insulin in a twice-per-day regimen allows injection closer to mealtime and improves post-prandial glycemic control without increasing the risk of hypoglycemia.", "A variety of abnormalities of metabolic, haemostatic and endothelial markers are associated with Type 2 diabetes. Evidence suggests that poor post-prandial blood glucose control may contribute to vascular risk. We aimed to examine whether the restoration of a more physiological insulin profile post-prandially would improve these abnormalities. Twenty-one patients with insulin-treated Type 2 diabetes were recruited into a single centre, crossover, double-blind study. Patients were randomized to unmodified human insulin or insulin aspart before main meals for 6-week study periods, both together with NPH insulin. At the end of each study period, pre-breakfast levels of markers of vascular risk were assessed and a test meal performed. There was no significant difference in HbA(1c) (7.04 +/- 0.13% (+/-S.E.) versus 7.15 +/- 0.11%, P = 0.060) with insulin aspart compared to human insulin at the end of each study period. The mean post-prandial blood glucose concentration at 90 min from self-monitored results was lower with insulin aspart than with human insulin (7.9 +/- 0.4 mmol/l versus 9.3 +/- 0.4 mmol/l, P = 0.011) as was study day post-prandial blood glucose at 90 min (8.4 +/- 0.5 mmol/l versus 9.2 +/- 0.6 mmol/l, P = 0.046). No significant differences were found in fasting lipid profile, apolipoproteins, fibrinogen, plasminogen activator inhibitor-1, E-selectin, or homocysteine between the two study periods. Insulin aspart resulted in improved post-prandial glycaemic control when compared to human insulin in Type 2 diabetic patients, but this was not associated with changes in markers of vascular risk.", "Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin. Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion (CSII) treatment were assessed in an open randomized crossover trial comparing insulin lispro and regular human insulin, both applied with insulin pumps.\n A total of 113 type 1 patients (60 male, 53 female, age [mean +/- SD] 37 +/- 12 years, duration of diabetes 19 +/- 9 years) participated in this open, randomized crossover study. Both insulins were applied for 4 months each with the appropriate intervals between the prandial insulin bolus and the meal (human insulin: 30 min; lispro: 0 min). Observation parameters were HbA1c, daily and postprandial blood glucose profiles, adverse events, rate of hypoglycemic and hyperglycemic events, number of catheter obstructions, and treatment satisfaction as assessed with an international validated questionnaire.\n The patients were well controlled with a mean HBA1c of 7.24 +/- 1.0% at baseline. HbA1c decreased in both treatment periods, but it was better during insulin lispro treatment (insulin lispro: 6.8 +/- 0.9%, regular human insulin: 6.9 +/- 1.0%, Friedman's rank-sum test: P < 0.02). In addition, the 1-h and 2-h postprandial rises in blood glucose were significantly lower (P < 0.001 for each meal) with insulin lispro, resulting in smoother daily glucose profiles as compared with regular human insulin. No significant differences were reported for the rate of hypoglycemia (mean +/- SD [median]: insulin lispro 12.4 +/- 13.9 [8], regular human insulin 11.0 +/- 11.2 [8]), for the rate of catheter obstructions (42 events in each treatment arm), and for the number and type of adverse events. No severe case of ketoacidosis was seen during insulin lispro treatment, whereas one case was reported during therapy with regular human insulin. Treatment satisfaction was better when patients were treated with insulin lispro.\n Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment. Its safety profile does not differ from that of regular human insulin.", "To compare the efficacy and safety of preprandial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes.\n Open randomised multicentre study. Women were treated with multiple insulin injections aiming at normoglycaemia. Blood glucose was determined six times daily, HbA(1c) every 4 weeks. Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21, 28 and 34.\n 33 pregnant women with type 1 DM were randomised to treatment with lispro insulin (n=16) or regular insulin (n=17).\n Blood glucose was significantly lower (P<0.01) after breakfast in the lispro group, while there were no significant group differences in glycemic control during the rest of the day. Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia (blood glucose <3.0 mmol/l) was more frequent in the lispro than in the regular group (5.5 vs. 3.9%, respectively). HbA(1c) values at inclusion were 6.5 and 6.6% in the lispro and regular group respectively. HbA(1c) values declined during the study period and were similar in both groups. There was no perinatal mortality. Complications during pregnancy, route of delivery and foetal outcome did not differ between the groups. Retinopathy progressed in both groups, one patient in the regular group developed proliferative retinopathy.\n The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies.", "The objective of this study was to compare the efficacy of the rapid-acting Lys(B28), Pro(B29) human insulin analog, insulin lispro, with currently available short-acting human insulin in a multiple injection therapy (MIT) regimen with respect to blood glucose and plasma insulin profiles and to serum metabolites (lactate, free fatty acids, glycerol, and beta-hydroxybutyrate) in 12 well-controlled type 1 diabetic subjects (8 male, HbA1c 6.8 +/- 0.9% [mean +/- SD]).\n After a run-in period of 4 weeks, patients were treated with either lispro at mealtime or human insulin 30 min before the meal for two periods of 4 weeks in a randomized open-label crossover study. Intermediate-acting insulin (NPH insulin) was given at bedtime. At the end of both study periods, metabolic profiles were assessed from 10:00 P.M. to 7:00 P.M. the next day.\n During the treatment periods, glycemic control was stable during lispro but improved during human insulin (delta HbA1c lispro 0.1 +/- 0.48, NS; human insulin -0.41 +/- 0.34%, P < 0.05). Glucose excursions, as measured by the incremental AUC, during the day and for the 2-h postprandial periods, were lower, although not significantly, for lispro. Insulin profiles demonstrated a faster rise after administration of lispro as compared with human insulin, peaking at 61 +/- 11.9 and 111 +/- 48.1 min (P < 0.01). Glycerol levels showed a slight increase before lunch and dinner, suggestive of enhanced lipolytic activity and compatible with the lower insulin levels.\n Lispro insulin applied in an MIT regimen creates more physiologic insulin profiles and tends to lower the glycemic excursions during the day compared with short-acting insulin. The analog can be applied safely in an MIT regimen, with mealtime intervals up to 5 h.", "nan", "Lispro (LP) and regular human (HR) insulins were compared in Type 1 diabetic (T1DM) patients on either a Mediterranean diet or normal diet. Twelve T1DM patients were recruited and randomized into two groups of 6, groups A and B. They were treated in different sequences (in 3-month intervals for 1 year). Group A: LP insulin and normal diet, LP insulin and Mediterranean diet, regular insulin and Mediterranean diet, regular insulin and normal diet. Group B: regular insulin and normal diet, regular insulin and Mediterranean diet, LP insulin and Mediterranean diet, LP insulin and normal diet. Each patient was treated with rapid acting insulin, either LP insulin or HR insulin, before each main meal and a dose of slow acting insulin at bedtime. Every 15 days the glycemic control, the incidence and frequency of hypoglycemic episodes, and any adverse events were evaluated. Every 3 months, hematology and a chemistry panel, pre- and post-prandial glycemic and insulinemic profiles were evaluated in all patients. HbA1c levels significantly decreased in LP patients on normal diet, post-prandial glycemic levels were significantly lower in LP than in HR patients from 30 min onwards, 15-min post-prandial insulin levels higher in LP- than in HR-treated patients, and hypoglycemic episodes were significantly less in LP- than in HR-treated patients. LP insulin, irrespective of the type of diet, results in more effective glycemic control, significantly reduces hypoglycemic episodes as opposed to traditional insulin therapy and seems to be more effective with a normal diet than with a Mediterranean diet.", "To compare the safety and efficacy of insulin aspart (IAsp), buffered regular insulin (BR), and insulin lispro administered by continuous subcutaneous insulin infusion (CSII) in patients with type 1 diabetes.\n After completing a 4-week run-in period with BR, 146 adult patients with type 1 diabetes (with pretrial CSII experience) were randomly assigned (2:2:1) to CSII treatment with IAsp, BR, or lispro for 16 weeks in a multicenter, open-label, randomized, parallel-group study. Bolus insulin doses were administered 30 min before meals (BR) or immediately before meals (IAsp or lispro).\n Treatment groups had similar baseline HbA(1c) (7.3% +/- 0.7 for IAsp, 7.5% +/- 0.8 for BR, and 7.3% +/- 0.7 for lispro). After 16 weeks of treatment, HbA1c values were relatively unchanged from baseline, and the mean changes in baseline HbA1c values were not significantly different between the three groups (0.00 +/- 0.51, 0.15 +/- 0.63, and 0.18 +/- 0.84 for the IAsp, BR, and lispro groups, respectively). The rates of hypoglycemic episodes (blood glucose <50 mg/dl) per patient per month were similar (3.7, 4.8, and 4.4 for the IAsp, BR, and lispro groups, respectively). Clogs/blockages in pumps or infusion sets were infrequent; most subjects (76, 83, and 75% in the IAsp, BR, and lispro groups, respectively) had < or = 1 clog or blockage per 4 weeks during the trial.\n Insulin aspart in CSII was as efficacious and well tolerated as BR and lispro and is a suitable insulin for continuous subcutaneous insulin infusion using external pumps.", "Despite considerable experience with insulin lispro, few blinded comparisons with soluble insulin are available. This study compared insulin lispro with human soluble insulin in patients with Type 1 diabetes mellitus on multiple injection therapy who inject shortly before meals.\n Glucose control, frequency of hypoglycaemia and patient preference were examined in the course of a prospective, randomized, double-blind, crossover comparison, with a 6-week run-in period and 12 weeks on each therapy. Ninety-three patients took part, all on multiple daily doses of insulin, with soluble insulin before meals and NPH (isophane) insulin at night. The main outcome measures were self-monitored blood glucose profiles, glycated haemoglobin, frequency of hypoglycaemic episodes, patient satisfaction and well-being and patient preference.\n Blood glucose levels were significantly lower after breakfast and lunch, but higher before breakfast, lunch and supper, in patients taking insulin lispro. Levels of HbA(1c) were 7.4 +/- 1.1% on Humulin S and 7.5 +/- 1.1% on insulin lispro (P = 0.807). The overall frequency of symptomatic hypoglycaemia did not differ, but patients on insulin lispro were less likely to experience hypoglycaemia between midnight and 6 a.m., and more likely to experience episodes from 6 a.m. to midday. Questionnaires completed by 84/87 patients at the end of the study showed that 43 (51%) were able to identify each insulin correctly, nine (11%) were incorrect, and 32 (38%) were unable to tell the insulins apart. No significant preference emerged: 35 (42%) opted for insulin lispro, 24 (29%) opted for Humulin S, while the remainder had no clear preference.\n Substitution of insulin lispro for soluble insulin in a multiple injection regimen improved post-prandial glucose control at the expense of an increase in fasting and pre-prandial glucose levels. Patients who already injected shortly before meals expressed no clear preference for the fast-acting analogue, and did not improve their overall control as a result of using it. Nocturnal hypoglycaemia was however, less frequent on insulin lispro, and may emerge as a robust indication for its use.", "To compare the effects of Humalog Mix25 (Humalog Mix75/25 in the USA) (Mix25) and human insulin 30/70 (30/70) on the 24-hour inpatient plasma glucose (PG) profile in patients with type 2 diabetes mellitus (T2DM).\n A randomised, open-label, 8-week crossover study. Study insulins were injected twice daily, 5 minutes before breakfast and dinner.\n Four-week outpatient (dose-adjustment) treatment phase, and 3-day inpatient (test) phase.\n Twenty-five insulin-treated patients with T2DM (ages 40-66 years), mean (+/- standard error of the mean) (SEM) HbA1c 7.7% +/- 0.23%, and body mass index (BMI) 29.3 +/- 0.83 kg/m2.\n 24-hour PG profiles, PG excursions after meals, PG area under the curve (AUC), and 30-day hypoglycaemia rate.\n The 2-hour PG excursions following breakfast (5.5 +/- 0.34 v. 7.2 +/- 0.34 mmol/l, p = 0.002) and dinner (2.4 +/- 0.27 v. 3.4 +/- 0.27 mmol/l, p = 0.018) were smaller with Mix25 than with 30/70. PG AUC between breakfast and lunch was smaller with Mix25 than with 30/70 (77.6 +/- 3.8 v. 89.5 +/- 4.3 mmol/h/ml, p = 0.001). PG AUC between lunch and dinner, dinner and bedtime, and bedtime and breakfast did not differ between treatments. Pre-meal and nocturnal PG were comparable. The postprandial insulin requirement for lunch meals was supplied equally by the two insulin treatments. The thirty-day hypoglycaemia rate was low (Mix25 0.049 +/- 0.018 v. 30/70 0.100 +/- 0.018 episodes/patient/30 days, p = 0.586) for both treatments.\n In patients with T2DM, Mix25 improved the 24-hour PG profile with lower postprandial PG excursions than with human insulin 30/70.", "Insulin lispro is a human insulin analog that dissociates more rapidly than human regular insulin after subcutaneous injection, resulting in higher insulin levels at an earlier point in time and a shorter duration of action. The aim of the study was to evaluate if this pharmacokinetic difference would translate into better postprandial and overall control in 30 IDDM patients (age, 35.1 +/- 1.5 years; male-female ratio, 17:13; BMI, 24.8 +/- 0.5 kg/m2; HbA1c, 8.03 +/- 0.13% at baseline) treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) in a double-blind crossover clinical study. Patients were randomized to insulin lispro or human regular insulin for 3 months before crossing over to the other insulin for another 3 months. All meal boluses were given immediately before breakfast, lunch, and supper. An eight-point blood glucose profile was measured once weekly, and HbA1c levels were measured monthly. At the end of the 3-month treatment period, HbA1c levels were significantly lower with insulin lispro, compared with human regular insulin: 7.66 +/- 0.13 vs. 8.00 +/- 0.16% (P = 0.0041). While preprandial, bedtime, and 2:00 A.M. values for blood glucose were not significantly different, 1-h postprandial blood glucose was significantly improved after breakfast, lunch, and dinner with insulin lispro, compared with human regular insulin: 8.35 vs. 9.79 mmol/l (P = 0.006), 7.58 vs. 8.74 mmol/l (P = 0.049), and 7.85 vs. 9.01 mmol/l (P = 0.03). The incidence of hypoglycemia per 30 days (blood glucose levels, <3.0 mmol/l) was 8.4 +/- 1.3 before randomization, decreasing to 6.0 +/- 0.9 for insulin lispro and to 7.6 +/- 1.3 for regular insulin during the last month of the study. Two patients in each group reported insulin precipitation. We conclude that insulin lispro improves glycemic control in CSII without increasing the risk of hypoglycemia.", "To compare glycemic control obtained with the new rapid-acting insulin analog insulin aspart with that obtained with unmodified human insulin using algorithm-driven dosage adjustment.\n This was a multicenter randomized double-blind crossover study of 90 male subjects with type 1 diabetes. Insulin aspart or soluble human insulin was administered before meals, and NPH insulin was administered at bedtime as basal therapy. Each 4-week study period ended with a 24-h inpatient serum insulin and plasma glucose profile.\n The 24-h plasma glucose control obtained with insulin aspart, as assessed by excursions of blood glucose outside a predefined normal range (4.0-7.0 mmo/l), was superior (22% reduction in excursion, P < 0.01). Fructosamine levels remained unchanged with insulin aspart, with daytime glycemic control superior but nighttime glycemic control inferior. Eight-point home blood glucose profiles confirmed that insulin aspart significantly improved postprandial blood glucose control after lunch and dinner (P < 0.05) without deterioration of preprandial blood glucose control. Hypoglycemic episodes requiring third-party intervention were significantly fewer with insulin aspart than with human insulin (20 vs. 44 events, P < 0.002). Insulin aspart was well tolerated.\n In comparison with human insulin, insulin aspart can improve postprandial glycemic control as assessed by a reduction in hyper- and hypoglycemic excursions in people with type 1 diabetes. For its full potential to be realized, it will need to provide better control of nighttime hyperglycemia.", "To study whether post-prandial insulin lispro (PL) could be used as a part of insulin therapy instead of premeal human regular insulin (HR) in prepubertal children with Type 1 diabetes mellitus (Type 1 DM).\n In this open, randomized cross-over study patients used either PL or HR at breakfast and at dinner. After a 1-month screening period, patients were randomized to treatment with PL or HR for 3 months and then they crossed over to the other insulin for an additional 3 months. The patients were 24 prepubertal children with Type 1 DM (median age 6.2 years, duration of diabetes 37 months). Home monitoring of 1-day glucose profiles at meals (premeal, 1 h and 2 h after breakfast and after dinner) and HbA1c were measured before randomization, before cross-over, and at the last visit. Data on hypoglycaemic episodes were collected at each of the seven visits. The variables were compared between the two treatments.\n Of the patients 22/24 completed the study. There were no major differences in the glucose excursions between PL and HR after breakfast (mean +/- SD: 1-h PL 3.7 +/- 4.7 vs. HR 2.9 +/- 3.9 mmol/l, P = 0.3; 2-h -0.9 +/- 5.4 vs. 0.3 +/- 4.5 mmol/l, P = 0.2, respectively) or after dinner (1-h PL -2.5 +/- 4.8 vs. HR -0.4 +/- 3.7 mmol/l, P = 0.07, 2-h -4.1 +/- 5.2 vs. -0.7 +/- 5.0 mmol/l, P = 0.05, respectively). Mean change of HbA1c was similar in both treatment groups (PL 0.2 +/- 0.8% vs. HR -0.4 +/- 0.7%, P = 0.1). The frequency of hypoglycaemic episodes was 4.9 per patient per month during treatment with PL, and 4.4 during HR (P = 0.3).\n Treatment with post-prandial lispro as a meal insulin is as effective and safe as traditional treatment with regular insulin in young children.", "To compare the plasma glucose (PG) response with a fixed mixture of 25% insulin lispro and 75% NPL (Mix25), prior to a meal and 3 h before exercise, to human insulin 30/70 (30/70) in patients with type 2 diabetes.\n Thirty-seven patients were treated in a randomized, open-label, 8-week, two-period crossover study. Mix25 was injected 5 min before breakfast and dinner throughout the study, as was 30/70 on inpatient test days and on outpatient dose titration days. Following the 4-week outpatient phase, patients were hospitalized, and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30 min, separated by 30 min rest, starting 3 h after a 339 kcal breakfast.\n The 2-h postprandial PG was significantly lower with Mix25 ((mean +/- SEM) 10.5 +/- 0.4 mmol/l vs 11.6 +/- 0.4 mmol/l; p = 0.016). Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 (-3.6 +/- 0.29 mmol/l vs -4.7 +/- 0.31 mmol/l; p = 0.001). The maximum decrease in PG over 6 h, after exercise onset, was significantly less with Mix25 (-4.3 +/- 0.4 mmol/l vs -5.9 +/- 0.4 mmol/l; p < 0.001). The frequency of hypoglycemia (blood glucose (BG) < 3 mmol/l or symptoms) during the inpatient test was not different between treatments. During the outpatient phase, the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 (0.7 +/- 0.2 episodes/30 d vs 1.2 +/- 0.3 episodes/30 d; p = 0.042).\n Mix25 resulted in better postprandial PG control without an increase in exercise-induced hypoglycemia. The smaller decrease in PG during the postprandial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70, especially for patients in tight glycemic control.", "To compare quality of life (QoL) and treatment satisfaction in patients with Type 1 diabetes receiving the rapid-acting insulin analogue, insulin aspart (IAsp), with that in patients receiving soluble human insulin (HI).\n In this 6-month, multinational, randomized, open-label trial, 424 patients from German-speaking countries were subjected to psychometric assessment before and after randomization (ratio 2 : 1) to basal-bolus treatment with either IAsp (n = 283) or HI (n = 141). Patients on HI were advised to keep an injection-meal interval of 30 min, whereas patients on IAsp were advised to inject immediately before meals. Treatment satisfaction and diabetes-related QoL were assessed using validated instruments to measure the domains of patients' individual treatment goals, physical complaints, worries about the future, social relations, leisure time flexibility, daily hassles, diet restrictions, burdens and fear of hypoglycaemia, blood glucose fluctuations, self-efficacy, and fear of insulin analogues.\n After 6 months, IAsp was associated with significantly greater improvement in treatment satisfaction than HI in two different scales (P < 0.01), and in QoL with respect to diet restrictions (P < 0.01). Improved satisfaction was mainly due to increased dietary and leisure time flexibility (P < 0.0001). Twenty-three percent of the IAsp group vs. 14% of the HI group achieved small but important improvements of total QoL (between-group difference, P < 0.06). The number needed to treat (NNT) with IAsp for an important increase in QoL was calculated to be 10. Regression analyses of potential predictors of improvement in QoL highlighted patients intensely striving for physical strength (P < 0.01; NNT = 7) and patients feeling less protected against hypoglycaemia (P < 0.005; NNT = 8) as being the most likely to benefit from IAsp.\n Under these study conditions, IAsp improved treatment satisfaction and quality of life regarding diet restrictions when compared with human insulin. The 'numbers needed to treat' for important quality of life benefits indicate that the effect of IAsp in this regard is not trivial.", "The short-acting insulin analogue lispro ([LYS(B28), PRO(B29)] is absorbed from the subcutis more rapidly than soluble insulin (S). To compare the clinical effectiveness of lispro vs S, 11 Type 1 patients using continuous subcutaneous insulin infusion (CSII) therapy (6 F, 5 M, age 30 +/- 2.5 years, diabetes duration 14 +/- 1.0 years, BMI 24.0 +/- 0.8 kg m(-2), HbA1c 6.5 +/- 0.2%) were studied in an open, randomized, crossover study for 6 months (3 months lispro and 3 months S or vice versa). During lispro treatment mean fasting and 2 h postprandial blood glucose were lower compared to the S phase (fasting 6.5 +/- 0.4 vs 7.5 +/- 0.4 mmol l(-1) (NS), postprandial 6.8 +/- 0.3 vs 8.3 +/- 0.3 mmol l(-1), p = 0.03). In patients treated first with lispro HbA1c levels improved from 6.3 +/- 0.2% to 5.7 +/- 0.3%; On reversion to S HbA1c increased to 6.2 +/- 0.2%. In the group treated first with S, HbA1c fell (6.7 +/- 0.4% vs 6.5 +/- 0.3%) and then improved further to 6.3 +/- 0.3% with lispro. None of these changes were significant. There was no significant difference with respect to hypoglycaemic or other adverse events. It can be concluded that lispro in CSII therapy is safe and may improve postprandial glucose excursions.", "This study compared the glucose-lowering effect of insulin lispro, given before or after meals, with regular human insulin given before meals in prepubertal children with diabetes.\n A 3-way crossover, open-label study involving 61 prepubertal children (ages 2.9-11.4 years) with type 1 diabetes. The children were randomly assigned to receive regular human insulin 30 to 45 minutes before meals, insulin lispro within 15 minutes before or immediately after meals, combined with basal insulin. Each treatment lasted 3 months. Hemoglobin A(1c) levels and home glucose monitoring profiles were measured at the end of each treatment period.\n Treatment with insulin lispro before breakfast resulted in lower 2-hour postprandial glucose values than regular human insulin (11.7 +/- 4.4 mmol/L vs 15.0 +/- 5.4 mmol/L). Similarly, insulin lispro given before dinner resulted in lower blood glucose values 2 hours postprandially (8.8 +/- 5.0 mmol/L vs 10.8 +/- 5.4 mmol/L) than regular human insulin. When insulin lispro was administered after meals, the 2-hour glucose levels were between those seen with either insulin lispro or regular human insulin given before meals. The number and types of adverse events, the rates of hypoglycemia, and the HbA(1c) levels did not differ among the 3 therapies.\n In prepubertal children, insulin lispro given before meals is safe and significantly lowers postprandial glucose levels after breakfast and dinner compared with regular human insulin, and insulin lispro given after the meal provides similar benefits as regular human insulin before the meal.", "Insulin lispro was compared with regular human insulin with respect to glycaemic control in patients with diabetes mellitus on intensive insulin treatment. Sixty-two patients (55 type 1; 7 type 2) from eight study centres in the Czech Republic, Slovenia and the Slovak Republic participated in a 4-month, open-label, randomized, crossover study. Patients administered insulin lispro immediately before meals or regular human insulin 30 min before meals. A test meal (220-400 kcal), based on local and individual dietary habits and consistent for each patient throughout the study was given at baseline and at the end of each treatment. At each test meal visit HbA1c, fasting blood glucose, 1-hour and 2-hour postprandial blood glucose levels were measured. The level of HbA1c (7.6% +/- 1.5% versus 7.4% +/- 1.5%), incidence of hypoglycaemia (41-66% of patients--versus 39-63%) and daily insulin dose (0.67 +/- 0.11 U/kg versus 0.65 +/- 0.11 U/kg) did not differ between treatment groups at endpoint (insulin lispro versus regular human insulin, respectively). Mean 2-hour postprandial blood glucose excursion for the insulin lispro group (0.0 +/- 3.7 mmol/L) was significantly lower (p = 0.035) when compared with the regular human insulin group (1.3 +/- 3.7 mmol/L) at endpoint. Therapy with insulin lispro was therefore associated with a significant improvement in postprandial blood glucose excursion control when compared with regular human insulin, without an increase in rate of hypoglycaemia.", "To compare the efficacy of insulin aspart, a rapid-acting insulin analogue, with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus.\n Prospective, multi-centre, randomized, open-labelled, parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1,070 adult subjects with Type 1 diabetes. Study patients were randomized 2:1 to insulin aspart or unmodified human insulin before main meals, with NPH-insulin as basal insulin. Main outcome measures were blood glucose control as assessed by HbA1c, eight-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia, and adverse events.\n After 6 months, insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 (95% confidence interval 0.03-0.22) %Hb, P < 0.02. Eight-point blood glucose profiles showed lower post-prandial glucose levels (mean baseline-adjusted -0.6 to -1.2 mmol/l, P < 0.01) after all main meals, but higher pre-prandial glucose levels before breakfast and dinner (0.7-0.8 mmol/l, P < 0.01) with insulin aspart. Satisfaction with treatment was significantly better in patients treated with insulin aspart (WHO Diabetes Treatment Satisfaction Questionnaire (DTSQ) baseline-adjusted difference 2.3 (1.2-3.3) points, P < 0.001). The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 (0.59-1.18, NS). Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart (1.3 vs. 3.4% of patients, P < 0.05), as were late post-prandial (4-6 h) events (1.8 vs. 5.0% of patients, P < 0.005).\n These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control, hypoglycaemia, and quality of life, in people with Type 1 diabetes mellitus.", "To compare the effects of insulin lispro (LP) and human regular insulin (HR) when given twice daily with NPH insulin on glycemic control (HbA1c), daily blood glucose profiles and rates of hypoglycemia in patients with type 2 diabetes mellitus after failure to respond to sulfonylurea drugs.\n A 5.5-month randomized, open-label, parallel study of 148 patients receiving either LP (n = 70) or HR (n = 78). Eight-point blood glucose profiles and HbA1c measurements were collected at baseline, 1.5, 3.5 and 5.5 months.\n Two-hour post-breakfast and 2-hour post-supper blood glucose levels (means [and standard errors]) were significantly lower for LP than for HR at the end point (9.5 [0.4] mmol/L v. 10.9 [0.4] mmol/L and 8.4 [0.4] mmol/L v. 9.7 [0.4] mmol/L, respectively, p = 0.02 in both cases). HbA1c improved from 10.5% (0.2%) (LP) and 10.3% (0.2%) (HR) to 8.0% (0.1%). Hypoglycemia rates were similar during the day; however, there was an overnight trend to reduced rates with LP (0.08 [0.03] episodes/30 d v. 0.16 [0.04] episodes/30 d, p = 0.057). Quality-of life assessment showed significant improvement (p < 0.05) in the diabetes-related worry scale for LP subjects whereas HR subjects slightly worsened.\n With traditional twice-daily insulin administration algorithms, LP improves 2-hour postprandial glucose levels, quality of life and overnight hypoglycemia rates while delivering an equivalent level of glycemic control (HbA1c) compared with HR to insulin-naïve patients with type 2 diabetes who require insulin.", "To compare the safety, efficacy and management of insulin lispro (LP) with regular human insulin (RH) in young diabetic children treated with continuous subcutaneous insulin infusion (CSII).\n 27 very young diabetic children (age 4.6 +/- 2.2 years) treated with CSII participated in an open-label, randomized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH.\n Mean daily basal rate was significantly higher during the LP period (p = 0.04). No differences were seen in changes in HbA1c levels, number of hypoglycemic events, cutaneous infections and catheter occlusions. There was no significant difference between the two treatments for preprandial and postprandial glucose values, although prandial glucose excursions tended to be lower with LP (significant at dinner, p = 0.01). Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy (p < 0.05). No episode of ketoacidosis occurred during LP treatment. More parents indicated that LP made their own and the child's daily life easier (p = 0.02) and preferred LP (p = 0.01).\n LP in CSII therapy in children is safe, as effective as RH, improved postprandial excursions, met the needs of young children in their daily life well, and gained their parents' satisfaction and preference. However, a shorter duration of LP resulted in hyperglycemia during the first part of the night, which must be compensated for by increasing nocturnal basal rates during this time.", "While lispro insulin has been reported to lower postprandial blood glucose concentrations, less consistent effects have been shown for glycosylated hemoglobin (HbA1c) levels. Aim of this study was to determine whether pre-meal association of NPH, an intermediate-acting insulin, with lispro improves overall glycemic control in type 1 diabetic patients.\n Eighty-five type 1 diabetic patients were studied in a multicenter randomized comparative (human regular vs lispro insulin) crossover (3-month) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary. The number of injections was kept constant: 42% and 58% of patients injected insulin 3 and 4 times per day, respectively. Fasting and preprandial blood glucose levels were similar, while postprandial levels improved after lispro compared to human regular insulin (breakfast: 8.28 +/- 2.39 vs 9.28 +/- 2.72 mmol/l; lunch: 8.33 +/- 2.67 vs 9.06 +/- 2.67 mmol/l, dinner: 8.06 +/- 2.72 vs 9.28 +/- 2.44 mmol/l, ANOVA: p = 0.003). HbA1c also improved after lispro: 8.1 +/- 0.9 vs 8.3 +/- 0.8%, p < 0.05. The rate of hypoglycemia was similar. Patients showed better acceptance of lispro treatment (p < 0.001).\n Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia. This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long.", "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.", "It has been found that non-fasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. The main aim of treatment of type 2 diabetic patients is to control plasma glucose and HbA1c levels. In this study, we aimed to assess the effects of three different insulin regimens (group I: lispro insulin + NPH insulin, group II: lispro insulin + metformin and group III: regular insulin + NPH insulin) on overall glycaemic control and metabolic parameters in type 2 diabetic patients with secondary oral anti-diabetic drug failure.\n Sixty type 2 diabetic patients with secondary OAD failure were randomly allocated into three different treatment groups equally. There were no significant differences between groups concerning age, body mass index, diabetes duration, HbA1c and serum lipid levels at the beginning of the study. During the 6-month treatment period, blood glucose levels were determined 10 times during 24 h at pre-meal, post-prandial 1 and 2 h and at bedtime.\n Group I was found to be the most effective treatment regimen in controlling HbA1c levels (group I vs. group II, p = 0.013; group I vs. group III, p = 0.001; group II vs. group III, p > 0.05). When the comparison was made in each group, change in HbA1c was statistically significant for all groups (-3.18%, p = 0.001; -2.02%, p = 0.043 and -2.66%, p = 0.008 respectively). Group I was found to be more effective in controlling fasting and post-prandial plasma glucose levels measured at all times during the day when compared with group II and group III. In group II triglyceride levels were found to be significantly reduced, whereas other groups had no effect on lipids. No serious hypoglycaemic episodes were observed in any of the cases, whereas in group I hypoglycaemic episode rates were increased (chi2 = 8.843, p = 0.012).\n Lispro insulin plus NPH insulin regimen is more effective in controlling both pre- and post-prandial glucose levels and HbA1c when compared to regular insulin plus NPH insulin combination. Mealtime lispro insulin plus metformin combination therapy should also be seriously considered as an effective and alternative treatment regimen. It is worthy of attention that insulin lispro plus metformin lowered triglyceride levels.", "Because there are limited data on the comparison of insulin aspart and mixed insulin in type 2 diabetes, this trial was performed to compare the efficacy and safety of preprandial insulin aspart with human soluble insulin (HI) and human premix (70% NPH/30% regular) insulin (MIX).\n A total of 231 type 2 diabetic patients were randomized to insulin aspart (n = 75), HI (n = 80), or MIX (n = 76) for 3 months. Insulin aspart and HI were administered with or without bedtime NPH insulin. A total of 204 patients completed the trial according to protocol. HbA1c, 7-point blood glucose, insulin dosage, and hypoglycemic episodes were recorded. The primary end point was \"change of HbA1c\" from baseline to last visit. Analysis for equivalence was performed by t tests with three subtests.\n HbA1c decreased 0.91 +/- 1.00 for insulin aspart, 0.73 +/- 0.87 for HI, and 0.65 +/- 1.10 for MIX with the following confidence intervals: insulin aspart HI (-0.21 to 0.57, P = 0.025), insulin aspart MIX (-0.17 to 0.69, P = 0.092), and HI-MIX (-0.33 to 0.48, P = 0.006). Postprandial blood glucose decreased in the insulin aspart group: 0.44 mmol/l to >1.67 mmol/l compared with HI and 1.1 mmol/l to >1.67 mmol/l compared with MIX. Preprandial insulin doses were similar in the insulin aspart and HI groups (10-14.5 U). Hypoglycemic events per month were 0.56 HI, 0.40 insulin aspart, and 0.19 MIX.\n Statistically, insulin aspart was not equivalent to another treatment in terms of HbA1c reduction. Insulin aspart treatment resulted in improved HbA1c and postprandial blood glucose. The application of insulin aspart was safe and well tolerated.", "Several studies have suggested that use of the short-acting insulin analog, insulin lispro, in multiple injection therapy may reduce the risk of hypoglycemia in comparison with regular insulin. This effect might be more pronounced in well-controlled patients, since intensive treatment of IDDM increases the rate of severe hypoglycemic events. This study evaluated the effects of insulin lispro on glycemic control and hypoglycemia rates in well-controlled IDDM patients.\n This was an open, randomized, 6-month crossover study of 199 IDDM patients. Glycemic control was evaluated by HbA1c, home blood glucose measurements, and rate and timing of hypoglycemic events. At the end of the study, patients completed an evaluation form regarding therapy-related quality of life.\n HbA1c remained constant at approximately 7.3% throughout the study. Meal-related glucose excursions were significantly lower with insulin lispro compared with regular insulin (mean -0.8 +/- 1.7 vs. 1.1 +/- 1.6 mmol/l, P < 0.001), as was the within-day variability (M value 27.7 +/- 19.7 vs. 30.2 +/- 23.1, P = 0.007). The incidence of severe hypoglycemic events (58 vs. 36, P = 0.037) including coma (16 vs. 3, P = 0.004) was significantly lower with insulin lispro than with regular insulin. Patients felt that insulin lispro increased flexibility and freedom of lifestyle.\n In well-controlled IDDM patients, insulin lispro is associated with a lower risk of severe hypoglycemia and coma." ]	Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child.
CD008194	[ "16322168", "15671460" ]	[ "A randomized, controlled trial of the effectiveness of community-based case management in insuring uninsured Latino children.", "The State Children's Health Insurance Program: a multicenter trial of outreach through the emergency department." ]	[ "Lack of health insurance adversely affects children's health. Eight million US children are uninsured, with Latinos being the racial/ethnic group at greatest risk for being uninsured. A randomized, controlled trial comparing the effectiveness of various public insurance strategies for insuring uninsured children has never been conducted.\n To evaluate whether case managers are more effective than traditional methods in insuring uninsured Latino children.\n Randomized, controlled trial conducted from May 2002 to August 2004.\n A total of 275 uninsured Latino children and their parents were recruited from urban community sites in Boston.\n Uninsured children were assigned randomly to an intervention group with trained case managers or a control group that received traditional Medicaid and State Children's Health Insurance Program (SCHIP) outreach and enrollment. Case managers provided information on program eligibility, helped families complete insurance applications, acted as a family liaison with Medicaid/SCHIP, and assisted in maintaining coverage.\n Obtaining health insurance, coverage continuity, the time to obtain coverage, and parental satisfaction with the process of obtaining insurance for children were assessed. Subjects were contacted monthly for 1 year to monitor outcomes by a researcher blinded with respect to group assignment.\n One hundred thirty-nine subjects were assigned randomly to the intervention group and 136 to the control group. Intervention group children were significantly more likely to obtain health insurance (96% vs 57%) and had approximately 8 times the adjusted odds (odds ratio: 7.78; 95% confidence interval: 5.20-11.64) of obtaining insurance. Seventy-eight percent of intervention group children were insured continuously, compared with 30% of control group children. Intervention group children obtained insurance significantly faster (mean: 87.5 vs 134.8 days), and their parents were significantly more satisfied with the process of obtaining insurance.\n Community-based case managers are more effective than traditional Medicaid/SCHIP outreach and enrollment in insuring uninsured Latino children. Case management may be a useful mechanism to reduce the number of uninsured children, especially among high-risk populations.", "We evaluated emergency department (ED)-based outreach for the State Children's Health Insurance Program (SCHIP).\n We conducted a multicenter trial among uninsured children (< or = 18 years) who presented to 5 EDs in 2001 and 2002. On-site staff enrolled consecutive subjects for a control period followed by an intervention period during which staff handed out SCHIP applications to the uninsured. The primary outcome was state-level confirmation of insured status at 90 days.\n We followed 223 subjects (108 control, 115 intervention) by both phone interview and state records. Compared to control subjects, those receiving a SCHIP application were more likely to have state health insurance at 90 days (42% vs 28%; P<.05; odds ratio [OR]=3.8; 95% confidence interval [CI]=1.7, 8.6). Although the intervention effect was prominent among 118 African Americans (50% insured after intervention vs 31% of controls, P<.05), lack of family enrollment in other public assistance programs was the primary predictor of intervention success (OR=3.7; 95% CI=1.6, 8.4).\n Handing out insurance applications in the ED can be an effective SCHIP enrollment strategy, particularly among minority children without connections to the social welfare system. Adopted nationwide, this simple strategy could initiate insurance coverage for more than a quarter million additional children each year." ]	The two studies included in this review provide evidence that in the US providing health insurance information and application assistance, and handing out application materials in hospital emergency departments can probably both improve insurance coverage of children. Further studies evaluating the effectiveness of different outreach strategies for expanding health insurance coverage of children in different countries are needed, with careful attention given to study design.
CD000505	[ "671204", "683224", "8477163", "463541", "7666265" ]	[ "Umbilical artery catheters: high, low, or no.", "Low positioning of umbilical-artery catheters increases associated complications in newborn infants.", "Randomized trial of umbilical arterial catheter position: clinical outcome.", "Umbilical artery catheterization in newborns. I. Thrombosis in relation to catheter type and position.", "The association of heparin exposure with intraventricular hemorrhage among very low birth weight infants." ]	[ "nan", "We performed a randomized prospective study of the effect of placement position of umbilical-artery catheters on complication rates in high-risk newborn infants. A higher complication rate (31 of 40 vs. 13 of 33) (P less than 0.005) occurred in the group with the catheter tip at the third to fourth lumbar segment, as compared to those with the tip at the seventh to eighth thoracic segment, owing to more episodes of blanching and cyanosis of the extremities. There was no difference between groups in the rate of complications requiring catheter removal. Aortography revealed thrombosis in 21 of 23 patients studied, but there was no clinical evidence of impaired circulation. In retrospect, we found that, independently of catheter position, administration of antibiotics through the catheter was associated with an increased rate of complications (63 vs. 20 per cent). Umbilical-artery catheterization entails potential risks regardless of the position of the catheter; placement of the catheter with its tip at the seventh to eighth thoracic segment may be associated with fewer complications than at lower positions.", "In order to determine if umbilical arterial catheter position affects the incidence of necrotizing enterocolitis, clinical outcome was analysed in 308 infants whose umbilical arterial catheter had been randomly allocated to a high (n = 162) or a low (n = 146) position. Necrotizing enterocolitis was classified as suspected or confirmed; all renal, lower limb and local catheter complications were also recorded. High umbilical arterial catheters were in place for longer than low catheters, provided more samples and were removed as an emergency less often. Lower limb blanching and cyanosis were more common with low catheters. Eleven cases of confirmed necrotizing enterocolitis occurred in the \"high\" group and nine in the \"low\" group. One case of fatal aortic thrombosis was encountered in the high group. Positioning umbilical arterial catheters in a high position allowed longer functional use and did not increase the incidence of necrotizing enterocolitis.", "Seventy-one sick newborn infants, who had an umbilical artery catheterized, were randomized in one of four catheter groups: long end-hole-, short end-hole-, long side-hole- or short side-hole catheter. A long catheter means a high position of the catheter tip (Th6--11) and a short catheter a low position of the tip (L3--5). An angiography through the indwelling catheter in order to diagnose thrombosis was performed before the catheter was withdrawn. Dissection of the aorta and its brances was performed on infants who died. The total frequency of thromboses was 26%. There were no thromboses among infants with long end-hole catheters while infants with short end-hole catheters had thrombosis in 26%, long side-hole catheters in 33% and short side-hole catheters in 64%. Long end-hole catheters functioned better than the others. Only 6 of 16 infants with thrombosis had physical signs from the legs, while 12 infants without thrombosis had similar signs.", "To determine whether there is a relationship between exposure to heparin and an increased risk of intraventricular hemorrhage (IVH), we analyzed data from a cohort of infants who had been subjects in a randomized clinical trial of umbilical artery catheter placement. Data from 862 infants who survived the first 6 days of life were used for analysis. The incidence of IVH (grades 1 through 4) was 28.6%. The mean (SD) birth weight for infants with IVH was 954 gm (247 gm) compared with 1053 gm (253 gm) among infants without IVH (p < 0.01). The mean (SD) heparin intake among infants with an IVH was 83.5 units/kg/day (48.7) compared with 59.4 units/kg/day (48.7) among infants without an IVH (p < 0.01). With the use of logistic regression modeling to adjust for a number of potentially confounding variables, including fluid intake and birth weight, we observed an odds ratio for an IVH of 1.96 (95% confidence interval = 1.32, 2.91) for infants with second through fourth quartile intakes of heparin compared with that for infants with first quartile heparin intakes. Although we cannot rule out the possibility that the observations from this model may be confounded by factors associated with the severity of illness of the infant, these data support the findings of previous reports of an association between heparin exposure and the risk for an IVH." ]	There appears to be no evidence to support the use of low placed umbilical artery catheters. High catheters should be used exclusively.
CD004493	[ "11291373", "2213870", "15376818", "8812826", "2057468", "17663611", "8757573", "3437450", "9786373", "12018753", "8435601", "16201856", "12509592", "10181020", "11550729", "12079251", "12612363", "11850136", "14636795", "7673531" ]	[ "The influence of a family program on adolescent tobacco and alcohol use.", "The efficacy of social-influence prevention programs versus \"standard care\": are new initiatives needed?", "Reducing the risks of alcohol use among urban youth: three-year effects of a computer-based intervention with and without parent involvement.", "Tobacco use measurement, prediction, and intervention in elementary schools in four states: the CATCH Study.", "The Tromsø Survey: the Family Intervention study--the effect of intervention on some coronary risk factors and dietary habits, a 6-year follow-up.", "An adaptive approach to family intervention: linking engagement in family-centered intervention to reductions in adolescent problem behavior.", "Long-term follow-up of the Busselton six-year controlled trial of prevention of children's behavior disorders.", "How generalizable are the effects of smoking prevention programs? Refusal skills training and parent messages in a teacher-administered program.", "Long-term effects of nurse home visitation on children's criminal and antisocial behavior: 15-year follow-up of a randomized controlled trial.", "Tobacco and alcohol use outcomes of a school-based intervention in New Delhi.", "Evaluation of two school smoking education programmes under normal classroom conditions.", "Effects of a controlled family-based health education/counseling intervention.", "Sustaining and broadening intervention impact: a longitudinal randomized trial of 3 adolescent risk reduction approaches.", "Effects of a school-based smoking prevention program among subgroups of adolescents.", "Randomized trial of brief family interventions for general populations: adolescent substance use outcomes 4 years following baseline.", "Longitudinal substance initiation outcomes for a universal preventive intervention combining family and school programs.", "Can parents who smoke socialise their children against smoking? Results from the Smoke-free Kids intervention trial.", "A randomized controlled trial of two primary school intervention strategies to prevent early onset tobacco smoking.", "A randomized trial of a family-based smoking prevention intervention in managed care.", "Preventing escalation in problem behaviors with high-risk young adolescents: immediate and 1-year outcomes." ]	[ "This study examined a family-directed program's effectiveness in preventing adolescent tobacco and alcohol use in a general population.\n Adolescents aged 12 to 14 years and their families were identified by random-digit dialing throughout the contiguous United States. After providing baseline data by telephone interviews, they were randomly allocated to receive or not receive a family-directed program featuring mailed booklets and telephone contacts by health educators. Follow-up telephone interviews were conducted 3 and 12 months after program completion.\n The findings suggested that smoking onset was reduced by 16.4% at 1 year, with a 25.0% reduction for non-Hispanic Whites but no statistically significant program effect for other races/ethnicities. There were no statistically significant program effects for smokeless tobacco or alcohol use onset.\n The family-directed program was associated with reduced smoking onset for non-Hispanic Whites, suggesting that it is worthy of further application, development, and evaluation.", "This study evaluates the effects of a school-based smoking prevention program after 1 year, using school (22 middle/elementary schools, 15 high schools) as both the unit of randomization and the unit of analysis. The multigrade level (grades 6 through 9) intervention was designed to address comprehensively the social influence factors that encourage smoking. Teacher survey data indicated that treatment schools had a median of 10 classroom sessions devoted to tobacco/drug use education, 5 of which were the sessions designed for this evaluation, and control schools had also dedicated a median of 10 classroom sessions to tobacco/drug education. Thus, the study evaluated the incremental effects of the social influence intervention compared to \"standard-care\" curricula. Among those who reported smoking one or more cigarettes in the month prior to the intervention, there was a significant treatment effect on rate of smoking at one year, but no grade level, gender, or interaction effects. The 1-year covariate-adjusted smoking rate among pretest smokers in the treatment schools was 76.6 cigarettes per month, compared to 111.6 cigarettes per month in control schools, a 31.4% difference. These effects were not accounted for by differential subject attrition. The analyses for nonsmokers, however, showed no significant effects, and the program did not affect self-reported alcohol or marijuana use. Taken together with the results of other prevention studies, these results point to the need for the development and evaluation of new initiatives to prevent substance use.", "This study tested a CD-ROM intervention with and without a parent involvement component to reduce risk of alcohol use among an urban sample of early adolescents.\n Youths (N = 514, mean age 11.5 years at recruitment) were assigned randomly by community site to receive the CD-ROM intervention, the CD-ROM plus parent intervention, or no intervention. All youths completed pretest, posttest and three annual follow-up measurements. After pretesting, youths and parents received their respective interventions.\n Main effects of the intervention and for measurement occasion as well as interaction effects of the intervention by measurement occasion were seen for substance use and related outcomes. Over time, youths in all 3 groups reported increased use of alcohol, tobacco and marijuana; youths who received the interventions reported smaller increases than control youths. At 3-year follow-up, alcohol use was lower for CD-ROM plus parent intervention youths than for CD-ROM only youths, who, in turn, reported less use than controls. Cigarette use was lower for youths in either intervention group than in the control group at posttest and at 1-, 2- and 3-year follow-ups. Marijuana use was lower for youths in either intervention than for controls at 1-, 2- and 3-year follow-ups. Youths in both intervention groups outperformed control youths at posttest and at 1- and 3-year follow-ups on levels of negative and peer influence toward substance use. Finally, at the 3-year follow-up, youths in the CD-ROM plus parent intervention group reported more family involvement in their alcohol use prevention efforts than did youths in the CD-ROM group, who, in turn, reported more positive levels of family involvement than youths in the control group.\n Study findings modestly support the CD-ROM intervention with and without the parent intervention to reduce alcohol use risks among urban early adolescents.", "The Child and Adolescent Trial for Cardiovascular Health (CATCH) is a multistate field trial examining the effects of school environment, classroom curricula, and family intervention components in promoting the cardiovascular health of elementary school students. The purpose of this paper is to describe the CATCH tobacco use intervention and measurement, including the adoption of tobacco-free school policies.\n In this study, changes in school tobacco use policies and smoking experimentation among students were assessed. Smoking experimentation was measured in all CATCH schools when the students were in their fifth-grade year. A total of 6,527 subjects in 96 schools in California, Louisiana, Minnesota, and Texas answered questions about behaviors and potential correlates of smoking as part of the CATCH health behavior questionnaire in Spring 1994. School tobacco use policy, an important complement to classroom- and home-based prevention efforts, was promoted as part of the CATCH intervention. The degree to which such policy was implemented was measured using surveys of school officials.\n At the end of fifth grade, only 4.8% of the subjects indicated that they had experimented with tobacco. School intervention condition was not a factor in the prediction of experimentation. Those whose best friend or sibling smoked, or who had ready access to cigarettes in the home, were more likely to have experimented with smoking. In the 3 years of the study, the percentages of tobacco-free schools went up from 49.7 to 76.8%. Though differences in the rate of policy adoption could not be directly attributed to the CATCH intervention, the implementation of the tobacco-free schools' policies did vary substantially from state to state. Minnesota and Texas, with stronger state laws supporting local policy, had nearly completely smoke-free schools. In spite of a statewide tobacco control initiative, California was slower to implement school policies. Louisiana, which allows local decision making regarding smoking policy, had the most difficulty establishing a policy for all districts.\n Future studies should examine the impact of parallel policy interventions that are ongoing at both school and state levels. Tobacco-free policies appear to be a crucial part of school-based interventions and must be tailored to political and regional factors affecting a given school district.", "While most intervention studies on coronary heart disease have focused on the high-risk person only, the present study used the family as the unit of intervention. In the study 1373 high-risk men, ages 30-54 years, were identified on the basis of high total cholesterol (TC) and/or low relative high-density lipoprotein cholesterol (HDL-C) (HDL-C/TC) following the 1979/1980 survey in Tromsø. The men and their families were randomly allocated to a control or intervention condition. The intervention families were given advice on diet, smoking, and exercise. At rescreening in 1986/1987, significantly lower risk factor levels were found in both the intervention men and their spouses compared with those in the control group. For children, the differences were small and mostly nonsignificant. Men, spouses, and children in the intervention group reported more favorable dietary habits than those in the control group. No differences were found in smoking or leisure time physical activity.", "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 reports the follow-up in 1993 of 209 adults, aged 27 to 29 years, who as children had been enrolled in a controlled trial of the prevention of children's behavior disorders. One hundred four control subjects and 105 study subjects, representing 90% of the original cohort, responded to a questionnaire detailing their present social situation and habits, educational achievements, and emotional well-being. The study subjects overall reported significantly fewer neurotic symptoms (p <0.001) than the control subjects; the study women also reported significantly fewer depressive symptoms (p <0.001). A greater proportion of the study subjects, compared with control subjects, had undertaken a university degree or diploma (p <0.013), whereas fewer of the men had attended a school of technology (p <0.049). The study women were less likely to be obese, as defined by a body mass index of 25 or more (p <0.030). The study men and women tended to smoke less than their control subjects, though significant differences were not attained. These results in the experimental group reflected the behavior patterns recorded at 6 years of age, after initial preschool interventional therapy. It appears that the initial benefit obtained from active counseling of mothers about their preschool children's behavior may be long lasting, favorably affecting the individuals' psychologic well-being, educational achievements, and social habits as adults.", "This study investigated both substantive and methodological issues associated with school-based smoking prevention programs. Substantive issues included the efficacy of a refusal skills training curriculum and of parent messages mailed to students' homes. Methodological issues included the effects of assigning classrooms versus entire schools to experimental conditions and determination of the effects of attrition on internal and external validity. Results revealed differential impact for different subgroups of adolescents. The refusal skills program produced lower rates of smoking than the control condition for students who were smokers at the pretreatment assessment but may have produced detrimental effects among males who were nonsmokers at pretest. The provision of parent messages did not affect outcome. Method of assignment (schools versus classrooms) failed to produce significant effects, and attrition did not affect internal validity. However, the above differential findings, as well as the impact of attrition on external validity, raise questions concerning the generalizability of smoking prevention programs.", "A program of home visitation by nurses has been shown to affect the rates of maternal welfare dependence, criminality, problems due to use of substances, and child abuse and neglect. However, the long-term effects of this program on children's antisocial behavior have not been examined.\n To examine the long-term effects of a program of prenatal and early childhood home visitation by nurses on children's antisocial behavior.\n Fifteen-year follow-up of a randomized trial. Interviews were conducted with the adolescents and their biological mothers or custodial parents.\n Semirural community in New York.\n Between April 1978 and September 1980, 500 consecutive pregnant women with no previous live births were recruited, and 400 were enrolled. A total of 315 adolescent offspring participated in a follow-up study when they were 15 years old; 280 (89%) were born to white mothers, 195 (62%) to unmarried mothers, 151 (48%) to mothers younger than 19 years, and 186 (59%) to mothers from households of low socioeconomic status at the time of registration during pregnancy.\n Families in the groups that received home visits had an average of 9 (range, 0-16) home visits during pregnancy and 23 (range, 0-59) home visits from birth through the child's second birthday. The control groups received standard prenatal and well-child care in a clinic.\n Children's self-reports of running away, arrests, convictions, being sentenced to youth corrections, initiation of sexual intercourse, number of sex partners, and use of illegal substances; school records of suspensions; teachers' reports of children's disruptive behavior in school; and parents' reports of the children's arrests and behavioral problems related to the children's use of alcohol and other drugs.\n Adolescents born to women who received nurse visits during pregnancy and postnatally and who were unmarried and from households of low socioeconomic status (risk factors for antisocial behavior), in contrast with those in the comparison groups, reported fewer instances (incidence) of running away (0.24 vs 0.60; P = .003), fewer arrests (0.20 vs 0.45; P = .03), fewer convictions and violations of probation (0.09 vs 0.47; P<.001), fewer lifetime sex partners (0.92 vs 2.48; P= .003), fewer cigarettes smoked per day (1.50 vs 2.50; P= .10), and fewer days having consumed alcohol in the last 6 months (1.09 vs 2.49; P = .03). Parents of nurse-visited children reported that their children had fewer behavioral problems related to use of alcohol and other drugs (0.15 vs 0.34; P = .08). There were no program effects on other behavioral problems.\n This program of prenatal and early childhood home visitation by nurses can reduce reported serious antisocial behavior and emergent use of substances on the part of adolescents born into high-risk families.", "To reduce tobacco use among adolescents.\n Thirty schools in New Delhi, India, were randomly assigned to 3 conditions: school-based and family-based intervention, school-based intervention only, or control group. Students were in the seventh grade at pretest (N = 4,776). The smoking intervention included posters, booklets, classroom activities, debates, and a signature campaign. The family intervention involved home activities. The survey measured tobacco knowledge, attitudes, offers, use, and intentions.\n Intervention students were significantly less likely than controls to have been offered, received, experimented with, or have intentions to use tobacco.\n The project had a significant impact on tobacco use.", "To assess the effectiveness of two school based smoking education projects in delaying onset of smoking behaviour and in improving health knowledge, beliefs, and values.\n Cluster randomised controlled trial of two projects taught under normal classroom conditions. Schools were allocated to one of four groups to receive the family smoking education project (FSE); the smoking and me project (SAM); both projects in sequence (FSE/SAM); or no intervention at all.\n 39 schools in Wales and England matched for size and catchment profile.\n All first year pupils in the schools were included and were assessed on three occasions (4538 before teaching (1988), 3930 immediately after teaching (1989), 3786 at one year follow up (1990)).\n Self reported smoking behaviour (backed by saliva sample) and change in relevant health knowledge, beliefs, and values.\n No consistent significant differences in smoking behaviour, health knowledge, beliefs, or values were found between the four groups. For never smokers at baseline the rate of remaining never smokers in 1990 was 74% (594/804) in the control group, 65% (455/704) in the FSE group, 70% (440/625) in the SAM group, and 69% (549/791) in the FSE/SAM group (chi 2adj = 6.1, df = 3, p = 0.1). Knowledge about effects of smoking rose in all groups from a mean score of 5.4 in 1988 to 6.4 in 1989 and 6.5 in 1990.\n More comprehensive interventions than school health education alone will be needed to reduce teenage smoking. Other measures including further restrictions on access to cigarettes and on the promotion of tobacco products need to be considered. Further research will be needed to develop effective school based health education projects, which should be formally field tested under normal conditions before widespread dissemination.", "To describe the effects of a controlled family-based health education/counseling intervention on health behaviors of children with a familial history of cardiovascular diseases (FH-CVDs).\n The intervention group (IG, n=432) received 5 counseling sessions. The control groups 1 (CG1, n=200) and 2 (CG2, n=423) received no counseling. Outcome measures comprised changes in diet, exercise, and cigarette smoking.\n The changes in the use of fats and salt, and in exercise, were more favorable in IG than in CG1 and/or CG2.\n Health education/counseling produced positive effects on diet and nutrition in particular and in part in exercise.", "To determine whether the addition of a parental monitoring intervention (Informed Parents and Children Together [ImPACT]) alone or with \"boosters\" could enhance (either broaden or sustain or both) the effect of a small group, face-to-face adolescent risk reduction intervention Focus on Kids (FOK).\n A longitudinal, randomized, community-based cohort study was conducted of 35 low-income, community-based, in-town settings. A total of 817 black youths aged 12 to 16 years at baseline were studied. After completion of baseline measures, youths were randomized to receive a face-to-face intervention alone (FOK only), a face-to-face intervention and a parental monitoring intervention (FOK plus ImPACT), or both of the above plus boosters (FOK plus ImPACT plus boosters). Risk and protective behaviors were assessed at 6 and 12 months after intervention.\n At 6 months' follow-up, youths in families that were assigned to FOK plus ImPACT reported significantly lower rates of sexual intercourse, sex without a condom, alcohol use, and cigarette use and marginally lower rates of \"risky sexual behavior\" compared with youths in families that were assigned to FOK only. At 12 months after intervention, rates of alcohol and marijuana use were significantly lower and cigarette use and overall risk intention were marginally lower among FOK plus ImPACT youths compared with FOK only youths. With regard to the boosters delivered at 7 and 10 months, 2 risk behaviors--use of crack/cocaine and drug selling--were significantly lower among the youths who were assigned to receive the additional boosters compared with youths without the boosters. The rates of the other risk behaviors and intentions did not differ significantly.\n The results of this randomized, controlled trial indicate that the inclusion of a parental monitoring intervention affords additional protection from involvement in adolescent risk behaviors 6 and 12 months later compared with the provision of an intervention that targets adolescents only. At the same time, the results of the present study do not provide sufficient evidence that booster sessions further improve targeted behaviors enough to include them in a combined parent and youth intervention.", "In autumn 1995 The Norwegian Cancer Society in cooperation with The Research Center for Health Promotion, University of Bergen started a study of school-based interventions aiming at preventing smoking among pupils in Norwegian secondary schools. The study comprised a nationwide sample of 4441 students at 99 schools (195 classes). This panel of students is followed through annual data collections till they graduate in spring 1997. Written consensus from students and parents was obtained from 95%. Schools were systematically allocated to one of four groups: Group A, control; Group B, intervention, containing classroom program, involvement of parents and teacher courses; Group C, like B, but without teacher courses; Group D, like B, but without parental involvement. Baseline data were collected by questionnaires administered in class in November 1994 and the first follow-up survey was carried out in May 1995. At follow-up the proportion of smokers had increased by 8.3 percentage points in Group A (control) and by 1.9 percentage points in Group B (most extensive intervention). As expected, the recruitment of smokers was higher in Groups C and D than in the ideal intervention, but lower than in the control group. Effects of the most extensive program among subgroups of students were examined by comparing Groups A and B. Students are categorized as high risk or low risk based on scores on scales measuring sensation seeking, physical maturity, antisocial behavior and parental smoking. The effect of the program on recruitment of smokers seems to have been at least as strong or even stronger among 'high-risk' students than among other students.", "This study examined the long-term substance use outcomes of 2 brief interventions designed for general population families of young adolescents. Thirty-three public schools were randomly assigned to 3 conditions: the 5-session Preparing for the Drug Free Years Program, the 7-session Iowa Strengthening Families Program, and a minimal contact control condition. The pretest involved 667 6th graders and their families. Assessments included multiple measures of initiation and current use of alcohol, tobacco, and marijuana. Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade. Significant intervention-control differences in initiation and current use were found for both interventions. It is concluded that brief family skills-training interventions designed for general populations have the potential to reduce adolescent substance use and thus have important public health implications.", "This study evaluated the substance initiation effects of an intervention combining family and school-based competency-training intervention components. Thirty-six rural schools were randomly assigned to 1 of 3 conditions: (a) the classroom-based Life Skills Training (LST) and the Strengthening Families Program: For Parents and Children 10-14, (b) LST only, or (c) a control condition. Outcomes were examined 1 year after the intervention posttest, using a substance initiation index (SII) measuring lifetime use of alcohol, cigarettes, and marijuana and by rates of each individual substance. Planned intervention-control contrasts showed significant effects for both the combined and LST-only interventions on the SII and on marijuana initiation. Relative reduction rates for alcohol initiation were 30.0% for the combined intervention and 4.1% for LST only.", "To evaluate Smoke-free Kids, a new home based programme to assist parents who smoke in socializing their children against smoking.\n Two year randomised controlled trial.\n At baseline, 887 adult smokers who had an abstinent child in the third grade (ages 7-8 years); 671 adults and children were retained through the 24 month follow up.\n Programme modules, newsletters, incentives, support calls.\n Anti-smoking socialisation; susceptibility to smoking.\n Of 327 parents randomised to treatment, 210 obtained adequate treatment by using at least three of five core modules. Programme efficacy analyses, which compared these parents with controls (n = 344), showed that exposure to adequate treatment predicted significantly higher levels in nearly all categories of anti-smoking socialisation three months post-intervention. Two years post-baseline, children of parents who reported adequate treatment scored significantly higher than controls on attributes that reduce susceptibility to smoking, and they scored significantly lower than controls on attributes that raise susceptibility to smoking. Programme effectiveness analyses compared all parents randomised to treatment (n = 327) with controls (n = 344). Treatment effects were evident for several socialisation outcomes; however, these effects were smaller and less consistent than those from the efficacy analyses. Similarly, although treated children scored higher than controls on attributes that reduce susceptibility and lower than controls on attributes that raise susceptibility, several of these between-group differences were not significant.\n Given adequate exposure to the Smoke-free Kids programme, significant beneficial effects were observed on anti-smoking socialisation in households where parents smoke cigarettes, and significant beneficial effects were observed on children's susceptibility to smoking after two years. Improving programme acceptance and utilisation is necessary before programme effectiveness can be demonstrated.", "In this article, we examine the impact of two universal, grade 1 preventive interventions on the onset of tobacco smoking as assessed in early adolescence. The classroom-centered (CC) intervention was designed to reduce the risk for tobacco smoking by enhancing teachers' behavior management skills in first grade and, thereby, reducing child attention problems and aggressive and shy behavior-known risk behaviors for later substance use. The family-school partnership (FSP) intervention targeted these early risk behaviors via improvements in parent-teacher communication and parents' child behavior management strategies. A cohort of 678 urban, predominately African-American, public school students were randomly assigned to one of three Grade 1 classrooms at entrance to primary school (age 6). One classroom featured the CC intervention, a second the FSP intervention, and the third served as a control classroom. Six years later, 81% of the students completed audio computer-assisted self-interviews. Relative to controls, a modest attenuation in the risk of smoking initiation was found for students who had been assigned to either the CC or FSP intervention classrooms (26% versus 33%) (adjusted relative risk for CC/control contrast=0.57, 95% confidence interval (CI), 0.34-0.96; adjusted relative risk for FSP/control contrast=0.69, 95% CI, 0.50-0.97). Results lend support to targeting the early antecedent risk behaviors for tobacco smoking.", "Each day more than 2000 youth under age 18 become daily smokers and the age of tobacco initiation has been going down. Health care settings can partner with families to encourage parent-child interactions that prevent youth tobacco use. This study evaluates a smoking prevention intervention package for parents and children (aged 10-12) provided through their managed care organization.\n A two-arm (usual care vs intervention) randomized trial was employed. The intervention included a mailed parental smoking prevention kit, outreach follow-up telephone calls to the parent by a health educator, child materials, medical record cues for physicians to deliver prevention messages, and parent newsletter. Outcome measures were susceptibility to smoking, experimentation with smoking, and smoking in the past 30 days as assessed by 20-month follow-up surveys of children.\n A total of 4,026 families enrolled in the study. The response rate to the 20-month follow-up was 88%. There were no significant effects of the intervention on any of the primary outcomes. The intervention was associated with modest but statistically significant increases in parent-child discussions of smoking related topics.\n A minimal-intensity family-based prevention program did not significantly reduce rates of susceptibility or tobacco use among youth aged 10-12 at baseline and 11 to 14 at follow-up. Development and evaluation of innovative approaches to tobacco use prevention must continue, despite our disappointing results. Parents and health care systems are too important to abandon as channels for prevention messages.", "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." ]	Some well-executed RCTs show family interventions may prevent adolescent smoking, but RCTs which were less well executed had mostly neutral or negative results. There is thus a need for well-designed and executed RCTs in this area.
CD003734	[ "5109955" ]	[ "Reduction of young driver crashes in a controlled pilot study: two-year follow-up in one Michigan high school." ]	[ "nan" ]	This systematic review provides no evidence that post-licence driver education is effective in preventing road traffic injuries or crashes. Although the results are compatible with a small reduction in the occurrence of traffic offences, this may be due to selection biases or bias in the included trials. Because of the large number of participants included in the meta-analysis (close to 300,000 for some outcomes) we can exclude, with reasonable precision, the possibility of even modest benefits.

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Dataset Card for MSLR2022

Dataset Summary

The Multidocument Summarization for Literature Review (MSLR) Shared Task aims to study how medical evidence from different clinical studies are summarized in literature reviews. Reviews provide the highest quality of evidence for clinical care, but are expensive to produce manually. (Semi-)automation via NLP may facilitate faster evidence synthesis without sacrificing rigor. The MSLR shared task uses two datasets to assess the current state of multidocument summarization for this task, and to encourage the development of modeling contributions, scaffolding tasks, methods for model interpretability, and improved automated evaluation methods in this domain.

Supported Tasks and Leaderboards

This dataset is used for the MSLR2022 Shared Task. For information on the shared task leaderboard, please refer here.

Languages

English

Dataset Structure

More information on dataset structure here.

Data Instances

MS^2

{
  "review_id": "30760312",
  "pmid": [
    "22776744",
    "25271670",
    "3493740",
    "1863023",
    "16291984",
    "23984728",
    "23996433",
    "18466198",
    "12151469",
    "27400308",
    "16053970",
    "22922316",
    "11897647",
    "11597664",
    "4230647"
  ],
  "title": [
    "Improved Cell Survival and Paracrine Capacity of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Promote Therapeutic Potential for Pulmonary Arterial Hypertension",
    "Adipose-derived stem cells attenuate pulmonary arterial hypertension and ameliorate pulmonary arterial remodeling in monocrotaline-induced pulmonary hypertensive rats",
    "Effect of bone marrow mesenchymal stem cells on experimental pulmonary arterial hypertension",
    "Survival in patients with primary pulmonary hypertension. Results from a national prospective registry.",
    "Sildenafil citrate therapy for pulmonary arterial hypertension.",
    "Macitentan and morbidity and mortality in pulmonary arterial hypertension.",
    "Long-term research of stem cells in monocrotaline-induced pulmonary arterial hypertension",
    "Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: open-label pilot study.",
    "Inhaled iloprost for severe pulmonary hypertension.",
    "Sildenafil reduces pulmonary vascular resistance in single ventricular physiology.",
    "Ambrisentan therapy for pulmonary arterial hypertension.",
    "Mesenchymal stem cell prevention of vascular remodeling in high flow-induced pulmonary hypertension through a paracrine mechanism.",
    "Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial.",
    "Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebocontrolled study",
    "SYRCLE\\u2019s risk of bias tool for animal studies"
  ],
  "abstract": [
    "Although transplantation of adult bone marrow mesenchymal stem cells ( BM-MSCs ) holds promise in the treatment for pulmonary arterial hypertension ( PAH ) , the poor survival and differentiation potential of adult BM-MSCs have limited their therapeutic efficiency . Here , we compared the therapeutic efficacy of human embryonic stem cell-derived MSCs ( hESC-MSCs ) with adult BM-MSCs for the treatment of PAH in an animal model . One week following monocrotaline (MCT)-induced PAH , mice were r and omly assigned to receive phosphate-buffered saline ( MCT group ) ; 3.0 \\u00d7 106 human BM-derived MSCs ( BM-MSCs group ) or 3.0 \\u00d7 106 hESC-derived MSCs ( hESC-MSCs group ) via tail vein injection . At 3 weeks posttransplantation , the right ventricular systolic pressure ( RVSP ) , degree of RV hypertrophy , and medial wall thickening of pulmonary arteries were lower= , and pulmonary capillary density was higher in the hESC-MSC group as compared with BM-MSC and MCT groups ( all p < 0.05 ) . At 1 week posttransplantation , the number of engrafted MSCs in the lungs was found significantly higher in the hESC-MSC group than in the BM-MSC group ( all p < 0.01 ) . At 3 weeks posttransplantation , implanted BM-MSCs were undetectable whereas hESC-MSCs were not only engrafted in injured pulmonary arteries but had also undergone endothelial differentiation . In addition , protein profiling of hESC-MSC- and BM-MSC-conditioned medium revealed a differential paracrine capacity . Classification of these factors into bioprocesses revealed that secreted factors from hESC-MSCs were preferentially involved in early embryonic development and tissue differentiation , especially blood vessel morphogenesis . We concluded that improved cell survival and paracrine capacity of hESC-MSCs provide better therapeutic efficacy than BM-MSCs in the treatment for PAH",
    "Abstract We investigated the effect of adipose-derived stem cells ( ADSCs ) transplantation effects on structural remodeling and pulmonary artery pressure in  monocrotaline (MCT)-induced pulmonary hypertensive rats . In the first experiment , 32 male Sprague-Dawley ( SD ) rats were r and omly divided into four groups ( n = 8/group ) : 3 ADSCs treated groups and normal control ( Ctrl ) . ADSCs were administered through the left jugular vein at 105 , 106 and 107 cells , respectively , and a cell density of 106cells/ml was shown to be optimal . The GFP-tagged ADSCs were identified in the lungs and differentiated into endothelial-like cells . In the second experiment , 96 male SD rats were r and omly divided into three groups ( n = 32/group ) : Ctrl , MCT-induced pulmonary arterial hypertension ( PAH ) , and PAH treated with ADSCs ( ADSCs ) . Two weeks post-MCT administration , the ADSCs group received 1 \\u00d7 106 ADSCs via the external jugular vein . Compared to PAH rats , mean pulmonary arterial pressure was decreased in rats at 1 , 2 , and 3 weeks after ADSCs-treatment ( 18.63 \\u00b1 2.15 mmHg versus 24.53 \\u00b1 2.90 mmHg ; 23.07 \\u00b1 2.84 mmHg versus 33.18 \\u00b1 2.30 mmHg ; 22.98 \\u00b1 2.34 mmHg versus 36.38 \\u00b1 3.28 mmHg , p < 0.05 ) . Meanwhile , the right heart hypertrophy index ( 36.2 1 \\u00b1 4.27 % versus 41.01 \\u00b1 1.29 % ; 39.47 \\u00b1 4.02 % versus 48.75 \\u00b1 2 .13 % ; 41.02 \\u00b1 0.9 % versus 50.52 \\u00b1 1.49 % , p < 0.05 , respectively ) , ratio of wall/lumen thickness , as well as the wall/lumen area were significantly reduced in PAH rats at these time points following ADSCs-treatment , as compared with untreated PAH rats . In summary , ADSCs may colonize the pulmonary arteries , attenuate pulmonary arterial hypertension and ameliorate pulmonary arterial remodeling",
    "The aim of the present study was to investigate the effect of bone marrow mesenchymal stem cell ( BMSC ) transp1antation on lung and heart damage in a rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension ( PAH ) . The animals were r and omly divided into 3 groups : control , PAH  and  BMSC implantation  groups . Structural changes in the pulmonary vascular wall , such as the pulmonary artery lumen area ( VA ) and vascular area ( TAA ) were measured by hematoxylin and eosin ( H&E ) staining , and the hemodynamics were detected by echocardiography . Two weeks post-operation , our results demonstrated that sublingual vein injection of BMSCs significantly attenuated the pulmonary vascular structural and hemodynamic changes caused by pulmonary arterial hypertension . The mechanism may be executed via paracrine effects",
    "OBJECTIVE To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival . DESIGN Registry with prospect i ve follow-up . SETTING Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart , Lung , and Blood Institute . PATIENTS Patients ( 194 ) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988 . MEASUREMENTS At diagnosis , measurements of hemodynamic variables , pulmonary function , and gas exchange variables were taken in addition to information on demographic variables , medical history , and life-style . Patients were followed for survival at 6-month intervals . MAIN RESULTS The estimated median survival of these patients was 2.8 years ( 95 % Cl , 1.9 to 3.7 years ) . Estimated single-year survival rates were as follows : at 1 year , 68 % ( Cl , 61 % to 75 % ) ; at 3 years , 48 % ( Cl , 41 % to 55 % ) ; and at 5 years , 34 % ( Cl , 24 % to 44 % ) . Variables associated with poor survival included a New York Heart Association ( NYHA ) functional class of III or IV , presence of Raynaud phenomenon , elevated mean right atrial pressure , elevated mean pulmonary artery pressure , decreased cardiac index , and decreased diffusing capacity for carbon monoxide ( DLCO ) . Drug therapy at entry or discharge was not associated with survival duration . CONCLUSIONS Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables : mean pulmonary artery pressure , mean right atrial pressure , and cardiac index . Such an equation , once vali date d prospect ively , could be used as an adjunct in planning treatment strategies and allocating medical re sources",
    "BACKGROUND Sildenafil inhibits phosphodiesterase type 5 , an enzyme that metabolizes cyclic guanosine monophosphate , thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells , including those in the lung . METHODS In this double-blind , placebo-controlled study , we r and omly assigned 278 patients with symptomatic pulmonary arterial hypertension ( either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts ) to placebo or sildenafil  ( 20 , 40 , or 80 mg ) orally three times daily for 12 weeks . The primary end point was the change from baseline to week 12 in the distance walked in six minutes . The change in mean pulmonary-artery pressure and World Health Organization ( WHO ) functional class and the incidence of clinical worsening were also assessed , but the study was not powered to assess mortality . Patients completing the 12-week r and omized study could enter a long-term extension study . RESULTS The distance walked in six minutes increased from baseline in all sildenafil groups ; the mean placebo-corrected treatment effects were 45 m ( + 13.0 percent ) , 46 m ( + 13.3 percent ) , and 50 m ( + 14.7 percent ) for 20 , 40 , and 80 mg of sildenafil , respectively ( P<0.001 for all comparisons ) . All sildenafil doses reduced the mean pulmonary-artery pressure ( P=0.04 , P=0.01 , and P<0.001 , respectively ) , improved the WHO functional class ( P=0.003 , P<0.001 , and P<0.001 , respectively ) , and were associated with side effects such as flushing , dyspepsia , and diarrhea . The incidence of clinical worsening did not differ significantly between the patients treated with sildenafil and those treated with placebo . Among the 222 patients completing one year of treatment with sildenafil monotherapy , the improvement from baseline at one year in the distance walked in six minutes was 51 m. CONCLUSIONS Sildenafil improves exercise capacity , WHO functional class , and hemodynamics in patients with symptomatic pulmonary arterial hypertension",
    "BACKGROUND Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point . We assessed the efficacy of macitentan , a new dual endothelin-receptor antagonist , using a primary end point of morbidity and mortality in a long-term trial . METHODS We r and omly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily , macitentan at a once-daily dose of 3 mg , or macitentan at a once-daily dose of 10 mg . Stable use of oral or inhaled therapy for pulmonary arterial hypertension , other than endothelin-receptor antagonists , was allowed at study entry . The primary end point was the time from the initiation of treatment to the first occurrence of a composite end point of death , atrial septostomy , lung transplantation , initiation of treatment with intravenous or subcutaneous prostanoids , or worsening of pulmonary arterial hypertension . RESULTS A total of 250 patients were r and omly assigned to placebo , 250 to the 3-mg macitentan dose , and 242 to the 10-mg macitentan dose . The primary end point occurred in 46.4 % , 38.0 % , and 31.4 % of the patients in these groups , respectively . The hazard ratio for the 3-mg macitentan dose as compared with placebo was 0.70 ( 97.5 % confidence interval [ CI ] , 0.52 to 0.96 ; P=0.01 ) , and the hazard ratio for the 10-mg macitentan dose as compared with placebo was 0.55 ( 97.5 % CI , 0.39 to 0.76 ; P<0.001 ) . Worsening of pulmonary arterial hypertension was the most frequent primary end-point event . The effect of macitentan on this end point was observed regardless of whether the patient was receiving therapy for pulmonary arterial hypertension at baseline . Adverse events more frequently associated with macitentan than with placebo were headache , nasopharyngitis , and anemia . CONCLUSIONS Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study . ( Funded by Actelion Pharmaceuticals ; SERAPHIN Clinical Trials.gov number , NCT00660179 . )",
    "Our previous studies have shown that bone marrow mesenchymal stem cells ( BMSCs ) can inhibit the progression of pulmonary artery hypertension ( PAH ) in the monocrotaline ( MCT ) model in the short term . The aim of this study was to further investigate the long-term effect of BMSCs on PAH and to explore the mechanism of the protective effect including the pulmonary vascular remodeling and cell differentiation . PAH model was established by subcutaneous injection of 50 mg/kg MCT as previously study . Postoperatively , the animals were r and omly divided into three groups ( n = 10 in each group ) : control , PAH group , and BMSCs implantation group . Six months after injection , immunology and immunohistochemistry analysis indicated the  MCT-induced intima-media thickness in muscular arteries was reduced ( P < 0.05 ) ; the area of collagen fibers in lung tissue was lower ( P < 0.05 ) , and the proliferating cell nuclear antigen level in pulmonary artery smooth muscle cells was decreased ( P < 0.05 ) . Immunofluorescence showed that the cells have the ability to differentiate between von Willebr and factor and vascular endothelial growth factor . Six months after intravenous injection , BMSCs could significantly improve pulmonary function by inhibiting the ventricular remodeling and the effect of cell differentiation",
    "Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs . In addition , our previous studies suggested that autologous EPC transplantation was feasible , safe , and might have beneficial effects on exercise capacity and pulmonary hemodynamics in adults with IPAH . Thus , we hypothesized that transplantation of EPCs would improve exercise capacity and pulmonary hemodynamics in children with IPAH . Thirteen children with IPAH received intravenous infusion of autologous EPCs . The right-sided heart catheterization and 6-MWD test were performed at baseline and at the time of 12 wk after cell infusion . At the time of 12 wk , mPAP decreased by 6.4 mmHg from 70.3 + /- 19.0 to 63.9 + /- 19.3 mmHg ( p = 0.015 ) . PVR decreased by approximately 19 % from 1118 + /- 537 to 906 + /- 377 dyn s/cm(5 ) ( p = 0.047 ) . CO increased from 3.39 + /- 0.79 to 3.85 + /- 0.42 L/min ( p = 0.048 ) . The 6-MWD increased by 39 m from 359 + /- 82 to 399 + /- 74 m ( p = 0.012 ) . NYHA functional class also improved . There were no severe adverse events with cell infusion . The small pilot study suggested that intravenous infusion of autologous EPCs was feasible , safe , and associated with significant improvements in exercise capacity , NYHA functional class , and pulmonary hemodynamics in children with IPAH . Confirmation of these results in a r and omized controlled trial are essential",
    "BACKGROUND Uncontrolled studies suggested that aerosolized iloprost , a stable analogue of prostacyclin , causes selective pulmonary vasodilatation and improves hemodynamics and exercise capacity in patients with pulmonary hypertension . METHODS We compared repeated daily inhalations of 2.5 or 5.0 microg of iloprost ( six or nine times per day ; median inhaled dose , 30 microg per day ) with inhalation of placebo .  A total of 203 patients with selected forms of severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension ( New York Heart Association [ NYHA ] functional class III or IV ) were included . The primary end point was met if , after week 12 , the NYHA class and distance walked in six minutes were improved by at least one class and at least 10 percent , respectively , in the absence of clinical deterioration according to predefined criteria and death . RESULTS The combined clinical end point was met by 16.8 percent of the patients receiving iloprost , as compared with 4.9 percent of the patients receiving placebo ( P=0.007 ) . There were increases in the distance walked in six minutes of 36.4 m in the iloprost group as a whole ( P=0.004 ) and of 58.8 m in the subgroup of patients with primary pulmonary hypertension . Overall , 4.0 percent of patients in the iloprost group ( including one who died ) and 13.7 percent of those in the placebo group ( including four who died ) did not complete the study ( P=0.024 ) ; the most common reason for withdrawal was clinical deterioration . As compared with base-line values , hemodynamic values were significantly improved at 12 weeks when measured after iloprost inhalation ( P<0.001 ) , were largely unchanged when measured before iloprost inhalation , and were significantly worse in the placebo group . Further significant beneficial effects of iloprost treatment included an improvement in the NYHA class ( P=0.03 ) , dyspnea ( P=0.015 ) , and quality of life ( P=0.026 ) . Syncope occurred with similar frequency in the two groups but was more frequently rated as serious in the iloprost group , although this adverse effect was not associated with clinical deterioration . CONCLUSIONS Inhaled iloprost is an effective therapy for patients with severe pulmonary hypertension",
    "BACKGROUND High pulmonary vascular resistance ( PVR ) may be a risk factor for early and late mortality in both Glen shunt and Fontan operation patients . Furthermore , PVR may increase long after the Fontan operation . Whether pulmonary vasodilators such as phosphodiesterase 5 inhibitors can decrease PVR in patients with single ventricular physiology remains undetermined . METHODS AND RESULTS This was a prospect i ve , multicenter study . Patients with single ventricular physiology who have a PVR index higher than 2.5 Wood units \\u00b7 \\u33a1 ( WU ) were enrolled .  Cardiac catheterization was performed before and after administration of sildenafil in all patients . After the Fontan operation , a  six minute walk test  ( 6MWT ) was also performed . A total of 42 patients were enrolled . PVR was significantly decreased in each stage of single ventricular physiology after sildenafil administration : from 4.3\\u00b11.5WU to 2.1\\u00b10.6WU ( p<0.01 ) in patients before a Glenn shunt , from 3.2\\u00b10.5WU to 1.6\\u00b10.6WU ( p<0.001 ) in patients after a Glenn shunt , and from 3.9\\u00b11.7WU to 2.3\\u00b10.8WU ( p<0.001 ) in patients after Fontan . In patients after Fontan , the 6MWT increased from 416\\u00b174 m to 485\\u00b172 m ( p<0.01 ) , and NYHA functional class improved significantly ( p<0.05 ) after sildenafil administration . No major side effects were observed in any patients . CONCLUSIONS Sildenafil reduced PVR in patients with single ventricle physiology . Sildenafil increased exercise capacity and improved NYHA functional class in patients after a Fontan operation . This implies that pulmonary vasodilation is a potential therapeutic target in selected patients with elevated PVR with single ventricle physiology . Long-term clinical significance warrants further study",
    "OBJECTIVES The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan , an oral endothelin type A receptor-selective antagonist , in patients with pulmonary arterial hypertension ( PAH ) . BACKGROUND Pulmonary arterial hypertension is a life-threatening and progressive disease with limited treatment options . Endothelin is a vasoconstrictor and smooth muscle cell mitogen that plays a critical role in the pathogenesis and progression of PAH . METHODS In this double-blind , dose-ranging study , 64 patients with idiopathic PAH or PAH associated with collagen vascular disease , anorexigen use , or human immunodeficiency virus infection were r and omized to receive 1 , 2.5 , 5 , or 10 mg of ambrisentan once daily for 12 weeks followed by 12 weeks of open-label ambrisentan . The primary end point was an improvement from baseline in 6-min walk distance ( 6MWD ) ; secondary end points included Borg dyspnea index , World Health Organization ( WHO ) functional class , a subject global assessment , and cardiopulmonary hemodynamics . RESULTS At 12 weeks , ambrisentan increased 6MWD ( + 36.1 m , p < 0.0001 ) with similar and statistically significant increases for each dose group ( range , + 33.9 to + 38.1 m ) . Improvements were also observed in Borg dyspnea index , WHO functional class , subject global assessment , mean pulmonary arterial pressure ( -5.2 mm Hg , p < 0.0001 ) , and cardiac index ( + 0.33 l/min/m2 , p < 0.0008 ) . Adverse events were mild and unrelated to dose , including the incidence of elevated serum aminotransferase concentrations > 3 times the upper limit of normal ( 3.1 % ) . CONCLUSIONS Ambrisentan appears to improve exercise capacity , symptoms , and hemodynamics in patients with PAH . The incidence and severity of liver enzyme abnormalities appear to be low",
    "UNLABELLED Pulmonary arterial hypertension ( PAH ) is characterized by functional and structural changes in the pulmonary vasculature , and despite the drug treatment that made significant progress , the prognosis of patients with advanced PH remains extremely poor . In the present study , we investigated the early effect of bone marrow mesenchymal stem cells ( BMSCs ) on experimental high blood flow-induced PAH model rats and discussed the mechanism . BMSCs were isolated , cultured from bone marrow of Sprague-Dawley ( SD ) rat . The animal model of PAH was created by surgical methods to produce a left-to-right shunt . Following the successful establishment of the PAH model , rats were r and omly assigned to three groups ( n=20 in each group ) : sham group ( control ) , PAH group , and BMSC group ( received a sublingual vein injection of 1 - 5 \\u00d7 10(6 ) BMSCs ) . Two weeks after the administration , BMSCs significantly reduced the vascular remodeling , improved the hemodynamic data , and deceased the right ventricle weight ratio to left ventricular plus septal weight ( RV/LV+S ) ( P<0.05 ) . Real-time reverse transcription-polymerase chain reaction ( RT-PCR ) and immunohistochemistry analysis results indicated that the inflammation factors such as interleukin-1\\u03b2 ( IL-1\\u03b2 ) , IL-6 , and tumor necrosis factor-\\u03b1 ( TNF-\\u03b1 ) were reduced ( P<0.05 ) ; the expression of matrix metallo proteinase-9 ( MMP-9 ) was lower ( P<0.05 ) ; vascular endothelial growth factor ( VEGF ) was higher in BMSC group than those in PAH group ( P<0.05 ) . CONCLUSION Sublingual vein injection of BMSCs for 2 weeks , significantly improved the lung and heart injury caused by left-to-right shunt-induced PAH ; decreased pulmonary vascular remodeling and inflammation ; and enhanced angiogenesis",
    "Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous prostacyclin has proven to be effective . However , this treatment requires a permanent central venous catheter with the associated risk of serious complications such as sepsis , thromboembolism , or syncope . Treprostinil , a stable prostacyclin analogue , can be administered by a continuous subcutaneous infusion , avoiding these risks . We conducted a 12-week , double-blind , placebo-controlled multicenter trial in 470 patients with pulmonary arterial hypertension , either primary or associated with connective tissue disease or congenital systemic-to-pulmonary shunts .  Exercise capacity improved with treprostinil and was unchanged with placebo ; the between treatment group difference in median six-minute walking distance was 16 m ( p = 0.006 ) . Improvement in exercise capacity was greater in the sicker patients and was dose-related , but independent of disease etiology . Concomitantly , treprostinil significantly improved indices of dyspnea , signs and symptoms of pulmonary hypertension , and hemodynamics . The most common side effect attributed to treprostinil was infusion site pain ( 85 % ) leading to premature discontinuation from the study in 8 % of patients . Three patients in the treprostinil treatment group presented with an episode of gastrointestinal hemorrhage . We conclude that chronic subcutaneous infusion of treprostinil is an effective treatment with an acceptable safety profile in patients with pulmonary arterial hypertension",
    "BACKGROUND Endothelin 1 , a powerful endogenous vasoconstrictor and mitogen , might be a cause of pulmonary hypertension . We describe the efficacy and safety of bosentan , a dual endothelin-receptor antagonist that can be taken orally , in patients with severe pulmonary hypertension . METHODS In this double-blind , placebo-controlled study , 32 patients with pulmonary hypertension ( primary or associated with scleroderma ) were r and omly assigned to bosentan ( 62.5 mg taken twice daily for 4 weeks then 125 mg twice daily ) or placebo for a minimum of 12 weeks . The primary endpoint was change in exercise capacity . Secondary endpoints included changes in cardiopulmonary haemodynamics , Borg dyspnoea index , WHO functional class , and withdrawal due to clinical worsening . Analysis was by intention to treat . FINDINGS In patients given bosentan , the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline , whereas it worsened by 6 m in those on placebo ( difference 76 m [ 95 % CI 12 - 139 ] , p=0.021 ) . The improvement was maintained for at least 20 weeks . The cardiac index was 1.0 L min(-1 ) m(-2 ) ( 95 % CI 0.6 - 1.4 , p<0.0001 ) greater in patients given bosentan than in those given placebo .  Pulmonary vascular resistance decreased by 223 dyn s cm(-)(5 ) with bosentan , but increased by 191 dyn s cm(-5 ) with placebo ( difference -415 [ -608 to -221 ] , p=0.0002 ) . Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class . All three withdrawals from clinical worsening were in the placebo group ( p=0.033 ) . The number and nature of adverse events did not differ between the two groups . INTERPRETATION Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension , suggesting that endothelin has an important role in pulmonary hypertension",
    "Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE \\u2019s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool  for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE \\u2019s RoB tool is an adapted version of the Cochrane RoB tool . Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies . This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the method ological quality of animal studies"
  ],
  "target": "Conclusions SC therapy is effective for PAH in pre clinical studies .\\nThese results may help to st and ardise pre clinical animal studies and provide a theoretical basis for clinical trial design in the future .",
  "background": "Background Despite significant progress in drug treatment , the prognosis of patients with advanced pulmonary arterial hypertension ( PAH ) remains extremely poor .\\nMany pre clinical studies have reported the efficacy of stem cell ( SC ) therapy for PAH ; however , this approach remains controversial .\\nThe aim of this systematic review and meta- analysis is to assess the potential efficacy of SC therapy for PAH .",
  "reviews_info": "Background Despite significant progress in drug treatment , the prognosis of patients with advanced pulmonary arterial hypertension ( PAH ) remains extremely poor .\\nMany pre clinical studies have reported the efficacy of stem cell ( SC ) therapy for PAH ; however , this approach remains controversial .\\nThe aim of this systematic review and meta- analysis is to assess the potential efficacy of SC therapy for PAH ."
}

Cochrane

{
  "review_id": "CD007697",
  "pmid": [
    "16394043"
  ],
  "title": [
    "Aggressive surgical effort and improved survival in advanced-stage ovarian cancer."
  ],
  "abstract": [
    "Residual disease after initial surgery for ovarian cancer is the strongest prognostic factor for survival. However, the extent of surgical resection required to achieve optimal cytoreduction is controversial. Our goal was to estimate the effect of aggressive surgical resection on ovarian cancer patient survival.\\n                A retrospective cohort study of consecutive patients with International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer undergoing primary surgery was conducted between January 1, 1994, and December 31, 1998. The main outcome measures were residual disease after cytoreduction, frequency of radical surgical resection, and 5-year disease-specific survival.\\n                The study comprised 194 patients, including 144 with carcinomatosis. The mean patient age and follow-up time were 64.4 and 3.5 years, respectively. After surgery, 131 (67.5%) of the 194 patients had less than 1 cm of residual disease (definition of optimal cytoreduction). Considering all patients, residual disease was the only independent predictor of survival; the need to perform radical procedures to achieve optimal cytoreduction was not associated with a decrease in survival. For the subgroup of patients with carcinomatosis, residual disease and the performance of radical surgical procedures were the only independent predictors. Disease-specific survival was markedly improved for patients with carcinomatosis operated on by surgeons who most frequently used radical procedures compared with those least likely to use radical procedures (44% versus 17%, P < .001).\\n                Overall, residual disease was the only independent predictor of survival. Minimizing residual disease through aggressive surgical resection was beneficial, especially in patients with carcinomatosis.\\n                II-2."
  ],
  "target": "We found only low quality evidence comparing ultra-radical and standard surgery in women with advanced ovarian cancer and carcinomatosis. The evidence suggested that ultra-radical surgery may result in better survival.\\u00a0 It was unclear whether there were any differences in progression-free survival, QoL and morbidity between the two groups. The cost-effectiveness of this intervention has not been investigated. We are, therefore, unable to reach definite conclusions about the relative benefits and adverse effects of the two types of surgery.\\nIn order to determine the role of ultra-radical surgery in the management of advanced stage ovarian cancer, a sufficiently powered randomised controlled trial comparing ultra-radical and standard surgery or well-designed non-randomised studies would be required."
}

Data Fields

MS^2

"review_id": The PubMed ID of the review.
"pmid": The PubMed IDs of the included studies.
"title": The titles of the included studies.
"abstract": The abstracts of the included studies.
"target": The conclusions, taken from the abstract of the review, that serve as the summarization target.
"background": A description of the reviews objective.

Cochrane

"review_id": The PubMed ID of the review.
"pmid": The PubMed IDs of the included studies.
"title": The titles of the included studies.
"abstract": The abstracts of the included studies.
"target": The conclusions, taken from the abstract of the review, that serve as the summarization target.

Data Splits

Each dataset is split into training, validation and test partitions

MS^2

train	validation	test
14188	2021	1667

Cochrane

train	validation	test
3752	470	470

Dataset Creation

Please refer to the following papers for details about dataset curation:

MSˆ2: A Dataset for Multi-Document Summarization of Medical Studies

Generating (Factual?) Narrative Summaries of RCTs: Experiments with Neural Multi-Document Summarization

Curation Rationale

[Needs More Information]

Source Data

Initial Data Collection and Normalization

[Needs More Information]

Who are the source language producers?

[Needs More Information]

Annotations

Annotation process

[Needs More Information]

Who are the annotators?

[Needs More Information]

Personal and Sensitive Information

[Needs More Information]

Considerations for Using the Data

Social Impact of Dataset

[Needs More Information]

Discussion of Biases

[Needs More Information]

Other Known Limitations

[Needs More Information]

Additional Information

Dataset Curators

[Needs More Information]

Licensing Information

Licensing information can be found here.

Citation Information

DeYoung, Jay, Iz Beltagy, Madeleine van Zuylen, Bailey Kuehl and Lucy Lu Wang. "MS2: A Dataset for Multi-Document Summarization of Medical Studies." EMNLP (2021).

@inproceedings{DeYoung2021MS2MS,
  title={MSˆ2: Multi-Document Summarization of Medical Studies},
  author={Jay DeYoung and Iz Beltagy and Madeleine van Zuylen and Bailey Kuehl and Lucy Lu Wang},
  booktitle={EMNLP},
  year={2021}
}

Byron C. Wallace, Sayantani Saha, Frank Soboczenski, and Iain James Marshall. (2020). "Generating (factual?) narrative summaries of RCTs: Experiments with neural multi-document summarization." AMIA Annual Symposium.

@article{Wallace2020GeneratingN,
  title={Generating (Factual?) Narrative Summaries of RCTs: Experiments with Neural Multi-Document Summarization},
  author={Byron C. Wallace and Sayantani Saha and Frank Soboczenski and Iain James Marshall},
  journal={AMIA Annual Symposium},
  year={2020},
  volume={abs/2008.11293}
}